Week 4

Inro

ow long can human cells survive? In the case of cancer, some types of cells might, in fact, be "immortal." Consider the cells of Henrietta Lacks, a young and very poor African American woman who died of cervical cancer in 1951. Cells taken from her original tumor, designated HeLa (from Henrietta Lacks) became the first human cells to easily grow in a laboratory. In their 60-plus years of survival, thousands of research projects have used these sturdy cells. Developing vaccines, studying drug effects, investigating virus behavior, developing tests for genetic disorders, and of course, research into cancer—these are only a few of their uses. They can be found in tissue culture laboratories all over the world, including those on the International Space Station. If you're interested in cell research, HeLa cells can even be purchased from catalogs. The message on Henrietta's tombstone is a fitting eulogy for this remarkable woman: In loving memory of a phenomenal woman, wife and mother who touched the lives of many. Here lies Henrietta Lacks (HeLa). Her immortal cells will continue to help mankind forever.

glands

A gland consists of one or more cells that produce and secrete a product. Most glands are composed primarily of epithelium in which the cells secrete their product by exocytosis. During secretion, the contents of a vesicle are released when the vesicle fuses with the plasma membrane. The mucus-secreting goblet cells within the columnar epithelium lining the digestive tract are single cells (see Fig. 4.4). Glands with ducts that secrete their product onto the outer surface (e.g., sweat glands and mammary glands) or into a cavity (e.g., pancreas) are called exocrine glands. Ducts can be simple or compound, as illustrated in Figure 4.18.

junctions

A tight junction forms an impermeable barrier because adjacent plasma membrane proteins actually join, producing a zipperlike fastening (Fig. 4.17a). In the stomach, digestive secretions are contained, and in the kidneys, the urine stays within kidney tubules because epithelial cells are joined by tight junctions. A gap junction forms when two adjacent plasma membrane channels join (Fig. 4.17b). This lends strength, but it also allows ions, sugars, and small molecules to pass between the two cells. Gap junctions in heart and smooth muscle ensure synchronized contraction. In an adhesion junction (desmosome), the adjacent plasma membranes do not touch but are held together by extracellular filaments firmly attached to cytoplasmic plaques, composed of dense protein material (Fig. 4.17c). Desmosomes that join heart muscle cells prevent the cells from tearing apart during contraction. Similarly, desmosomes in the cervix, the opening to the uterus (womb), prevent the cervix from ripping when a woman gives birth.

Tissues

A tissue is composed of specialized cells of similar structure that perform a common function in the body. There are four major types of tissues: (1) Epithelial tissue, also called epithelium, covers body surfaces and organs. It also lines body cavities and hollow body structures such as the heart, blood vessels, and digestive tract; (2) connective tissue binds and supports body parts; (3) muscular tissue contracts; (4) nervous tissue responds to stimuli and transmits signals from one body part to another. You can use the "4Cs" mnemonic to remember these functions: Tissues Cover-Connect-Contract-Communicate. Body organs are typically composed of all four tissue types. For example, the heart is covered by epithelium; its valves are supported by connective tissue; cardiac muscle pumps blood, and nerves regulate how rapidly the heart beats.

Blood

Blood (Fig. 4.12) is a connective tissue composed of formed elements suspended in a liquid matrix called plasma. There are three types of formed elements: red blood cells (erythrocytes), which carry oxygen; white blood cells (leukocytes), which aid in fighting infection; and platelets (thrombocytes), which are important to the initiation of blood clotting. Platelets are not complete cells; rather, they are fragments of giant cells called megakaryocytes, which are found in the bone marrow. In red bone marrow, stem cells continually divide to produce new cells that mature into the different types of blood cells. The rate of cell division is high because blood cells have a relatively short life span and must be replaced constantly. Blood is unlike other types of connective tissue because the extracellular matrix (plasma) is not made by the cells of the tissue. Plasma is a mixture of different types of molecules that enter blood at various organs

bone

Bone is the most rigid of the connective tissues. Two types of cells, the osteoblasts and osteocytes, form an extremely hard matrix of mineral salts, notably calcium salts, deposited around collagen fibers. The minerals give bone rigidity. The collagen fibers provide elasticity and strength, much like steel rods reinforce concrete. The outer portion of a long bone contains compact bone. Compact bone consists of many cylindrical-shaped units called osteons, or Haversian systems (Fig. 4.11). In an osteon, matrix is deposited in thin layers called lamellae that form a concentric pattern around tiny tubes called central canals. The canals contain nerve fibers and blood vessels. The blood vessels bring nutrients to bone cells (called osteocytes) that are located in small hollows called lacunae between the lamellae. The nutrients can reach all of the cells because minute canals (canaliculi) containing thin extensions of the osteocytes connect the osteocytes with one another and with the central canals. The ends of a long bone contain spongy bone, which has an entirely different structure. Spongy bone contains numerous bony bars and plates called trabeculae separated by irregular spaces (Fig. 4.11). Although lighter than compact bone, spongy bone is still designed for strength. Like braces used for support in buildings, the solid plates of spongy bone follow lines of stress. Blood cells are formed within red marrow found in spongy bone at the ends of certain long bones.

cardiac muscle

Cardiac muscle (Fig. 4.15) is found only in the walls of the heart. Its contraction pumps blood and accounts for the heartbeat. Cardiac muscle combines features of both smooth muscle and skeletal muscle. Like skeletal muscle, it has striations, but the contraction of the heart is involuntary (although the use of relaxation therapy does enable some people to consciously slowPage 76 the heart). Further, like skeletal muscle, its contractions are strong, but like smooth muscle, the contraction of the heart is inherent and rhythmical. Cardiac muscle contraction can be modified by the nervous and endocrine systems.

cut. membrane

Cutaneous Membrane The cutaneous membrane, or skin, forms the outer covering of the body. It consists of an outer portion of keratinized stratified squamous epithelium attached to a thick underlying layer of dense irregular connective tissue. The skin is discussed in detail in Chapter 5.

dense connective tissue

Dense connective tissue (Fig. 4.8) has a matrix produced by fibroblasts that contains thick bundles of collagen fibers. In dense regular connective tissue, the bundles are parallel as in tendons (which connect muscles to bones), ligaments (which connect bones to other bones at joints), and aponeuroses (sing., aponeurosis; which join muscle to muscle). In dense irregular connective tissue, the bundles run in different directions. This stretchy tissue is found in the inner portion of the skin (called the dermis) and in joint capsules (Fig. 4.9).

epith. tissues

Epithelial tissues share a set of common characteristics. In all epithelial tissues, the cells are tightly packed, with little space between them. Externally, this tissue protects the body from drying out, injury, and bacterial invasion. On internal surfaces, epithelial tissue protects, but it also may have an additional function. For example, epithelial tissue in the respiratory tract sweeps up impurities by means of cilia. Along the digestive tract, it secretes mucus, which protects the lining from digestive enzymes. In kidney tubules, its absorptive function is enhanced by the presence of fine, cellular extensions called microvilli. Epithelial cells readily divide to produce new cells that replace lost or damaged ones. Skin cells as well as those that line the stomach and intestines are continually being replaced. To support its very high rate of reproduction, epithelial tissue must get its nutrients from underlying connective tissues. Epithelial tissues are avascular—they lack blood vessels. Thus, they can be shed safely without the risk of bleeding. Because epithelial tissue covers surfaces and lines cavities, it always has a free surface. The other surface is attached to underlying tissue by a nonliving layer of carbohydrates and proteins called the basement membrane. Epithelial tissues are classified according to the shape of the cells and the number of cell layers (Table 4.1). A simple epithelium is composed of a single layer, and stratified epithelium is composed of two or more layers. Squamous epithelium has flattened cells; cuboidal epithelium has cube-shaped cells; and columnar epithelium has elongated cells. In addition, there are two specialized epithelial tissues: transitional epithelium and pseudostratified columnar epithelium.

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Even though cardiac muscle fibers are striated, the cells differ from skeletal muscle fibers in that they have a single, centrally placed nucleus. The cells are branched and seemingly fused to one another, and the heart appears to be composed of one large, interconnecting mass of muscle cells. Actually, cardiac muscle cells are separate and individual, but they are bound end-to-end at intercalated disks, areas where folded plasma membranes between two cells contain adhesion junctions and gap junctions (see page 75). These permit extremely rapid spread of contractile stimuli so that the fibers contract almost simultaneously.

schwann cells

Schwann cells are the neuroglia that enclose all long nerve fibers located outside the brain or spinal cord. Each Schwann cell covers only a small section of a nerve fiber. The gaps between Schwann cells are called nodes of Ranvier. Collectively, the Schwann cells provide nerve fibers with an insulating myelin layer, the myelin sheath, separated by the nodes. The myelin sheath speeds conduction because Page 78the nerve impulse jumps from node to node. Because the myelin sheath is white, all myelinated nerve fibers appear white.

tissues

Fibrous Connective Tissue Fibrous connective tissue includes both loose connective tissue and dense connective tissue. The body's membranes are composed of an epithelium and fibrous connective tissue (see pp. 80, 82). Loose connective tissue (also called areolar connective tissue) commonly lies between other tissues or between organs, binding them together. Areolar tissue has a fine, spider-web appearance. The cells of this tissue are mainly fibroblasts—large, star-shaped cells that produce extracellular fibers (Fig. 4.6). The cells are located some distance from one another because they are separated by a matrix with a jellylike ground substance containing many collagen and elastin fibers. The collagen fibers occur in bundles and are strong and flexible. The elastin fibers form a highly elastic network that returns to its original length after stretching. Adipose tissue (Fig. 4.7) is a type of loose connective tissue in which the fibroblasts enlarge and store fat, and there is limited extracellular matrix. Adipose protects and cushions many organs, including the eye and kidney. In addition, adipose stores energy and insulates the body against the cold.

3-D Printing to Create Complex Tissues

How would you construct a building? Start with aframework, or scaffold, formed from a strong, rigid material such as wood or steel. Around it, add layers: wood, brick, or metal, for example. Inside, insulate and add some form of finishing material (for example, wood or plaster). Now imagine a printer that will spray liquid materials—concrete, strong plastic materials, plaster—and build up that same house layer by layer. That's how a 3-D printer works, and many products such as automobile parts, tools, rocket components and household items are currently being manufactured in this way. Now, bioengineers are now exploring this new technology of 3-D printing to create functional tissues, layer by layer, using stem cells. Stem cells are so-called undifferentiated cells that can "change their minds"—that is, they can form multiple types of different cells. For several decades, scientists have been able to grow cells in simple sheets, in a process called tissue culture. (As you know from the chapter introduction, HeLa cells were the first to be easily grown in tissue culture.) Multiple applications are now widely used. For example, cultured cells can be grown from a burn patient's remaining healthy skin, then placed over the burned area as a skin graft. Bladder-shaped epithelial linings can be created using a connective tissue framework coated with the patient's own epithelial cells. The linings have been successfully transplanted into a patient's existing bladder. More recently, researchers used a framework created from a mouse heart that was stripped of its cells, and then coated with human heart cells. Not only did the cells grow, they beat in a coordinated way, much like the actual heart. Likewise, skeletal muscle cells grown on a framework were able to contract. Now imagine that tissue layers could be crafted into organs. As you know from Chapter 1, organs are created from layers of tissues. However, to grow an actual organ from tissue culture layers, a complex network of blood vessels would have to be simultaneously created to provide the organ with oxygen and nutrients, and to carry away waste. Bioengineers have now begun this organ creation process using 3-D printers and tissue-friendly inks called "bio-inks." Each ink performed a different function: one created a scaffold, a second contained living cells, and when complete, the third created a weblike network of tiny hollow tubes. Each bio-ink created its layers in a 3-D process. When the printing was complete, a three-layer tissue was created. Most important, the network of tubes was lined with simple squamous epithelium, just like a capillary (the smallest blood vessel) or a blood vessel lining. Scientists continue to develop and improve stem cell culture techniques, and refinements in 3-D printing of tissue scaffolds will likely happen as well. In the future, it may soon be possible to completely grow entire organs (such as a heart or a kidney) from the patient's own stem cells.

cartilage

In cartilage, the cells (chondrocytes), which lie in small chambers called lacunae, are separated by a matrix that is solid yet flexible. Immature chondrocytes, called chondroblasts, help cartilage to grow. Unfortunately, because this tissue lacks a direct blood supply, it heals very slowly if injured. The three types of cartilage are classified according to the type of fiber in the matrix. Hyaline cartilage (Fig. 4.10a) is the most common type of cartilage. It is strong and durable, yet flexible. The matrix, which contains only very fine collagen fibers, has a glassy, white, opaque appearance. This type of cartilage is found in the nose, at the ends of the long bones and ribs, and in the supporting rings of the trachea. The fetal skeleton is also made of this type of cartilage, although the cartilage is later replaced by bone. Elastic cartilage (Fig. 4.10b) has a matrix containing many elastic fibers, in addition to collagen fibers. For this reason, elastic cartilage is more flexible than hyaline cartilage. For example, elastic cartilage is found in the framework of the outer ear. Fibrocartilage (Fig. 4.10c) has a matrix containing strong collagen fibers. This type of cartilage absorbs shock, and is found in structures that withstand tension and pressure, such as the disks between the vertebrae in the backbone and the pads in the knee joint.

long axons...

Long axons are called fibers. In the brain and spinal cord, fibers form tracts. Outside the brain and spinal cord, fibers are bound together by connective tissue to form nerves. Nerves conduct signals from sense organs to the spinal cord and brain, where the phenomenon called sensation occurs. They also conduct nerve signals away from the spinal cord and brain to muscles, glands, and organs. In addition to neurons, nervous tissue contains neuroglia.

Simple cuboidal epithelium

Simple cuboidal epithelium (Fig. 4.3) consists of a single layer of cube-shaped cells attached to a basement membrane. This type of epithelium is frequently found in glands, such as salivary glands, the thyroid gland, and the pancreas, where its function is secretion. Simple cuboidal epithelium also covers the ovaries and lines most of the kidney tubules, the portion of the kidney where urine is formed. In one part of the kidney tubule, it absorbs substances from the tubule, and in another part it secretes substances into the tubule. Tubular absorption and secretion are both forms of active transport. Thus, the cuboidal epithelial cells contain many mitochondria, which supply the ATP needed for active transport. Additionally, where the cells function in reabsorption, microvilli (tiny, fanlike folds in the plasma membrane) increase the surface area of the cells.

membranes

Membranes Membranes line the internal spaces of organs and tubes that open to the outside, and they also line the body cavities discussed on pages 6-8. Mucous Membranes Mucous membranes line the interior walls of the organs and tubes that open to the outside of the body, such as those of the digestive, respiratory, urinary, and reproductive systems. These membranes consist of an epithelium overlying a layer of loose connective tissue. The epithelium contains goblet cells that secrete mucus. The mucus secreted by mucous membranes ordinarily protects interior walls from invasion by bacteria and viruses. For example, more mucus is secreted when a person has a cold, resulting in a "runny nose." In addition, mucus usually protects the walls of the stomach and small intestine from digestive juices, but this protection breaks down when a person develops an ulcer. Serous Membranes You'll remember from Chapter 1 (pages 6-7) that serous membranes line cavities, including the thoracic and abdominopelvic cavities, and cover internal organs such as the intestines. The term parietal refers to the wall of the body cavity, while the term visceral pertains to the internal organs. Therefore, parietal membranes line the interior of the thoracic and abdominopelvic cavities, and visceral membranes cover the organs. Serous membranes consist of a layer of simple squamous epithelium overlying a layer of loose connective tissue. They secrete serous fluid, which keeps the membranes lubricated. Serous membranes support the internal organs and tend to compartmentalize the large thoracic and abdominopelvic cavities. This helps to slow the spread of any infection. In the thorax, the pleurae are serous membranes that form a double layer around the lungs. The parietal pleura lines the inside of the thoracic wall, while the visceral pleura adheres to the surface of the lungs. Similarly, a double-layered serous membrane is a part of the pericardium, a covering for the heart (see Fig. 12.2). The peritoneum is the serous membrane within the abdomen. The parietal peritoneum lines the abdominopelvic wall, and the visceral peritoneum covers the organs. In between the organs, the visceral peritoneum comes together to form a double-layered mesentery that supports these organs (see Fig. 15.5).

muscle tissue

Muscular (contractile) tissue is composed of cells called muscle fibers (Table 4.3). Muscle fibers contain actin and myosin, which are protein filaments that interact to cause movement. The three types of vertebrate muscles are skeletal, smooth, and cardiac.

neuroglia

Neuroglia are cells that outnumber neurons nine to one and take up more than half the volume of the brain. The primary function of neuroglia is to nourish and support neurons. For example, types of neuroglia found in the brain are microglia, astrocytes, oligodendrocytes, and ependymal cells. Microglia, in addition to supporting neurons, engulf bacterial and cellular debris. Astrocytes provide nutrients to neurons and produce a hormone known as glial-derived growth factor, which someday might be used as a cure for Parkinson disease and other diseases caused by neuron degeneration. Oligodendrocytes form myelin, a protective layer of fatty insulation. Ependymal cells line the hollow cavities, or ventricles, of the brain.

nervous tissue

Page 77Nervous tissue, found in the brain and spinal cord, contains specialized cells called neurons that generate and conduct nerve signals. A neuron (Fig. 4.16) has three parts: (1) A dendrite receives signals that may result in a nerve signal; (2) the cell body contains the nucleus and most of the cytoplasm of the neuron; and (3) the axon conducts nerve impulses.

glands

Page 80Glands that no longer have a duct are appropriately known as the ductless glands, or endocrine glands. Endocrine glands (e.g., pituitary gland and thyroid) secrete their products internally so they are transported by the bloodstream. Endocrine glands produce hormones that help promote homeostasis. Each type of hormone influences the metabolism of a particular target organ or cells. Glands are composed of epithelial tissue, but they are supported by connective tissue, as are other epithelial tissues.

Pseudostratified Columnar Epithelium

Pseudostratified columnar epithelium is so named because it appears to be layered (pseudo, false; stratified, layers). However, true layers do not exist because each cell touches the basement membrane. Each cell is tapered and narrow at one end; the opposite end contains the nucleus. The irregular placement of the nuclei creates the appearance of several layers where only one really exists. Pseudostratified ciliated columnar epithelium (Fig. 4.5) lines parts of the reproductive tract as well as the air passages of the respiratory system, including the nasal cavities and the trachea (windpipe) and its branches. Mucus-secreting goblet cells are scattered among the ciliated epithelial cells. A surface covering of mucus traps foreign particles, and upward ciliary motion carries the mucus to the back of the throat, where it may be either swallowed or expectorated (spit out).

Simple squamous epithelium

Simple squamous epithelium is composed of a single layer of flattened cells, and therefore its protective function is not as significant as that of other epithelial tissues (Fig. 4.1). It is Page 67found in areas where simple diffusion occurs. (Remember that simple diffusion is movement of a substance from high to low concentration.) For example, simple squamous epithelium forms the tiny air sacs (called alveoli) of the lungs, where oxygen and carbon dioxide are exchanged. Capillaries (the smallest blood vessels) are tubes of simple squamous epithelium. Nutrients and wastes are exchanged between capillaries and neighboring cells by diffusion.

skeletal tissue

Skeletal muscle, also called voluntary muscle (Fig. 4.13), is attached by tendons to the bones of the skeleton, or directly to the skin. When skeletal muscle contracts, the muscle shortens, and body parts such as arms and legs move. Contraction of skeletal muscle is generally under one's conscious control. Skeletal muscle fibers are cylindrical and quite long—sometimes they Page 75run the length of the muscle. They arise during development when several cells fuse, resulting in one fiber with multiple nuclei. The nuclei are located at the periphery of the cell, just inside the plasma membrane. The fibers have alternating light and dark bands that give them a striated (striped) appearance. These bands are due to the placement of actin filaments and myosin filaments in the fiber, and they give skeletal muscle its strength.

smooth muscle

Smooth (visceral) muscle is so named because the arrangement of actin and myosin does not give the appearance of cross-striations. The spindle-shaped cells form layers in which the thick middle portion of one cell is opposite the thin ends of adjacent cells. (A spindle is a long, pointed, oval structure.) Consequently, the nuclei form an irregular pattern in the tissue (Fig. 4.14) Smooth muscle is not under conscious control and therefore is said to be involuntary. Smooth muscle is found in the walls of hollow structures and organs, such as the blood vessels, intestines, stomach, uterus, and urinary bladder. This muscle type contracts more slowly than skeletal muscle but can remain contracted for a longer time. Contractility is an important characteristic of smooth muscle, and it contracts rhythmically on its own. However, its contraction can be modified by the nervous and endocrine systems. Intestinal smooth muscle contracts in waves, thereby moving food along its lumen (central cavity). When the smooth muscle of blood vessels contracts, blood vessels constrict and their diameter decreases. This helps to regulate blood flow and blood pressure.

Differences

Stratified cuboidal epithelium is mostly found lining the larger ducts of certain glands, such as the mammary glands and the salivary glands. Often this tissue has only two layers. Page 68 Columnar Epithelium Simple columnar epithelium (Fig. 4.4) has cells that are longer than they are wide. They are modified to perform particular functions. Some of these cells are goblet cells that secrete mucus onto the free surface of the epithelium. This tissue is well known for lining digestive organs, including the small intestine, where microvilli expand the surface area and aid in absorbing the products of digestion. Simple columnar epithelium also lines the uterine tubes. Here, many cilia project from the cells and propel the egg toward the uterus, or womb. Stratified columnar epithelium is not very common but does exist in parts of the pharynx (back of the throat) and the male urethra.

Stratified squamous epithelium

Stratified squamous epithelium has many cell layers and does play a protective role (Fig. 4.2). While the deeper cells may be cuboidal or columnar, the outer layer is composed of squamous-shaped cells. (Note that stratified epithelial tissues are named according to the cells on their outer layer.) There are two forms of stratified squamous epithelium. The first is stratified squamous non-keratinized epithelium (Fig. 4.2a). This tissue acts as a lining for moist surfaces near the openings of body orifices, such as the mouth, vagina and anus. There, it protects against abrasion and drying out, or dessication. The second form of stratified squamous epithelium is the superficial (outer) portion of skin, which is keratinized (Fig. 4.2b). New skin cells produced in the basal (bottom) layer become reinforced by keratin, a protein that waterproofs and provides strength. As they move toward the skin's surface, the cells accumulate more and more keratin, and ultimately die. Thus, the outermost layer of skin is composed of dead cells, as you'll discover in Chapter 5.

Synovial Membranes

Synovial Membranes Synovial membranes line freely movable joint cavities and are composed of connective tissues. They secrete synovial fluid into the joint cavity. This fluid lubricates the ends of the bones so that they can move freely (see Fig. 6.21). In rheumatoid arthritis, the synovial membrane becomes inflamed and grows thicker. Fibrous tissue then invades the joint. The invading tissue may eventually become bony so that the bones of the joint are no longer capable of moving.

cancer 2

Targeting the Traitor Inside "When you get into a tight place and everything goes against you, till it seems as though you could not hang on a minute longer, never give up then, for that is just the place and time that the tide will turn." —Harriet Beecher Stowe, novelist A diagnosis of cancer is a terrifying event for anyone. Suddenly, life is turned upside-down, and decisions must quickly be made about treatment options. Radiation therapy and chemotherapy have existed for decades and continue to improve in effectiveness. However, these techniques are comparable to "carpet-bombing" in wartime—throwing many deadly bombs to blanket large areas and destroy as much as possible. As in a real-world conflict, chemotherapy and radiation therapy generally hit their cancer target, but they cause a lot of collateral damage. Frequently, these types of treatments cause extensive damage to other cells and tissues, which may be fatal. Furthermore, cancer cells from the original tumor that survive the original attack have also been observed to mutate over time, becoming increasingly stronger and resistant to both chemotherapy and radiation. When this occurs, these older techniques don't work, and the cancer returns. Discovering the Enemy Increasingly, oncologists (doctors who specialize in cancer treatment) have new options to offer their patients. One rapidly improving technique is to begin the treatment process by identifying the exact genetics of the patient's cancer cells. As you know from Focus on Forensics in Chapter 3, cellular DNA can be studied by creating a "fingerprint." Once the cancer is precisely identified, targeted therapies can be developed. Targeted therapies are sometimes referred to as the result of "rational drug design," because the treatments are tailored to damage or destroy only one type of cells—the cancer cells. Normal cells are largely unharmed, survival rates increase, side effects are reduced, and the patient's quality of life is improved. Page 81Targeted therapies work by directly interfering with cancer growth and progression. These treatments may function externally (directly on the plasma membrane, for example) or by obstructing internal metabolism. One of the first targeted therapies to be developed is directed at the cell membrane estrogen receptors of breast cancer cells. You discovered in Chapter 2 that estrogens stimulate the growth of all female structures. Unfortunately, breast cancer cells also increase their growth rate in response to estrogen. Selective estrogen receptor modulator (SERM) drugs block cancer cell estrogen receptors by binding to them in place of estrogen. Without estrogen as a promoter, cancer cell growth slows and sometimes completely stops. You may have heard of Tamoxifen, a commonly used SERM. Similar drugs are used for prostate, thyroid, and uterine cancers, and new receptor blockers aimed at other cancers are in development. Strengthening the Defense Many cancer researchers believe that cancer develops as a result of a patient's sluggish, underactive immune (defensive) system. Thus, stimulating a stronger immune response, called immunotherapy, is the strategy used in yet another type of targeted therapy. One existing immunotherapy involves using small immune system proteins called antibodies. Antibodies can be tailored to only bind on a specific set of cancer cells. One type simply "marks" the cancer cells when it attaches. Leukocytes then can destroy the cancer cell. (A good analogy for this process would be pinning a bull's-eye target to a wall—you'd know exactly where to aim!) Different antibodies are used to deliver toxic chemotherapy molecules precisely to specific cells, and others directly kill the cancer cell all by themselves. A currently used antibody (bevacizumab, marketed as Avastin®) blocks the action of VEGF, or vascular endothelial growth factor. VEGF is produced in huge quantities by cancer cells and stimulates nearby blood vessels to sprout new capillaries. Without VEGF, tumor cells starve and have no route to spread to other body areas. Bioengineers are now conducting clinical trials of a small, aspirin-sized sponge tablet that is implanted under the skin to fight melanoma, the deadliest form of skin cancer. Inside the tablet, the researchers place proteins obtained from the patient's tumor cells, along with a substance called granulocyte macrophage colony-stimulating factor (GMC-SF). This chemical attracts leukocytes, which quickly recognize the cancer proteins as foreign. These activated leukocytes then cause a potent immune response, which has actually stopped the melanoma in experimental animals. If it works as effectively on human melanoma, this approach could be used to fight this cancer and other cancer forms as well. Now imagine vaccinating people for cancer, using tumor cell vaccines that would work in a way similar to commonly used vaccines. For example, to immunize a person for the viral diseases hepatitis (a liver disease) and influenza (flu), a person is injected with pieces of virus. The virus segment can't cause disease, but it does alert the immune system to fight the virus if you're ever exposed. Recently, scientists developed a type of mouse cancer vaccine by mixing lab-grown leukocytes with tumor cell cultures. Exposing the two cell types to each other trained the leukocytes to recognize tumor cells, and the activated defense cells were then injected into the mice. After a second injection with more cancer cells, the resulting tumors in vaccinated mice were ten times smaller than those in unvaccinated mice. Much additional research and testing is needed, but human cancer vaccines created using similar techniques might be possible in the future. Destroying the Enemy Receptor-blocking drugs and antibodies can't enter the cancer cell, but modern small-molecule drugs are typically able to diffuse into the cell. Once inside, these drugs attack enzymes involved in cancer cell DNA replication, RNA transcription, or protein translation. (As you'll recall from Chapter 3, these three interphase processes are essential for the cell to reproduce.) Likewise, ongoing research is investigating nanoparticles to attack the cancer cell from inside. Nanoparticles are tiny, water-soluble shells roughly half the size of the smallest bacterial cell. These particles are filled with a chemotherapy drug, which spills out and kills the cancer cell once the cell takes up the nanoparticle by phagocytosis. (You also studied phagocytosis in Chapter 3.) Normally we think of viruses as enemies, because they are naturally occurring invaders that kill cells. However, cancer investigators are now using knowledge of their biology to develop strains that exclusively invade tumor cells. One strain under investigation delivers an inactive drug, called a prodrug, into colon cancer cells. Once inside, the prodrug activates and destroys the cell. Another genetically engineered virus that is currently in clinical trials selectively infects tumor cells of the liver, kidney, ovary, and skin. It then multiplies and destroys the cell while simultaneously triggering additional immune system activity. Winning the Fight Rational design therapies such as these may be used alone or combined with traditional chemotherapy and/or radiation based on the patient's own tumor cells. In the future, cancer scientists envision targeted viruses, small-molecule drugs, antibodies, and other new strategies to use in the fight against cancer. Hopefully, as research progresses, we will continue to see even more success stories: patients who have been completely cured.

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The cells of a tissue can function in a coordinated manner when the plasma membranes of adjoining cells interact. The junctions that occur between cells help cells function as a tissue.

fiber types

The fibers within the matrix are of three types. Collagen fibers contain the fibrous protein collagen, a substance that gives the fibers flexibility and tremendous strength. Elastic fibers contain the protein elastin, which is not as strong as collagen but is more elastic. Reticular fibers are very thin, highly branched, collagenous fibers that form delicate supporting networks.

Cancer

The life of almost every person has been touched, either directly or indirectly, by the specter of cancer. Cancer is not one disease, but perhaps several hundred diseases, all sharing a common characteristic: rapid, uncontrolled, and disorganized growth of tissue cells. Thus, any cell in any of the body's tissues can be the starting point for cancer. Cancers are classified according to the type of tissue from which they arise. Carcinomas, the most common type, are cancers of epithelial tissues (skin and linings); sarcomas are cancers that arise in connective tissue (muscle, bone, and cartilage); leukemias are cancers of the blood; and lymphomas are cancers of reticular connective tissue. The chance of cancer occurring in a particular tissue is related to the rate of cell division. As you know, epithelial cells reproduce at a high rate. That's why carcinomas account for 90% of all human cancers. In the body, a cancer cell divides to form a malignant neoplasm ("new tissue"), or a malignant tumor, that invades and destroys neighboring tissue. Cancer cells can also detach and spread to other sites by invading the blood vessels or the lymphatic vessels. Through this process, called metastasis, cancer tumors colonize healthy tissue elsewhere in the body. By contrast, noncancerous, or benign tumors are encapsulated (surrounded by a connective tissue capsule) and stay in one place. To support their growth, cancer cells release a growth factor that causes neighboring blood vessels to branch into the cancerous tissue, a process called vascularization. Cancer development seems to occur by a two-step process involving (1) initiation and (2) promotion. Cancer initiation is caused by a change, or a mutation, in the DNA (genes) of a cell, which results in runaway cell growth. Some mutations, such as those that result in certain forms of breast cancer, are genetically inherited. Agents that are known to actually cause DNA mutations are called carcinogens. Known carcinogens include viruses, excessive radiation, and certain chemicals. For example, cigarette smoke contains chemical carcinogens that may initiate cancers of the lung, throat, mouth, and urinary bladder. A cancer promoter is any influence that causes a mutated cell to start growing in an uncontrolled manner. A promoter might cause a second mutation or provide the environment for cells to form a tumor. For example, evidence suggests that a diet rich in saturated fats and cholesterol promotes colon cancer. Considerable time may elapse between initiation and promotion, and this is one reason why cancer is seen more often in older people. Cancer can be detected by physical examination, assisted by various means of viewing the internal organs. Mammograms can detect early breast cancer using low-level X ray, and thyroid cancer is diagnosed using radioactive iodine (see the Medical Focus on page 16). Specific blood tests exist for tumors that secrete a particular chemical in the blood. For example, the level of prostate-specific antigen (PSA) appears to increase in the blood according to the size of a prostate tumor. Tissue samples can also detect early malignancy. During a Pap smear (named for George Papanicolaou, the Greek doctor who first described the test), a small sample of epithelial tissue lining the cervix at the opening of the uterus is obtained using a cotton swab, then examined for cervical cancer cells. A biopsy is the removal of a suspect sample of tissue using a plunger-like device. A pathologist is a physician who is skilled at recognizing the abnormal characteristics that allow for cancer diagnosis. If cancer is found and treated before metastasis occurs, chances for a complete cure are greatly increased. Tumors can often be removed surgically, but there is always the danger that they have metastasized. For this reason, surgery is often preceded or followed by radiation therapy and/or chemotherapy to destroy rapidly dividing cancer cells. Radiation therapy using radioactive protons is preferred over X ray because proton beams can be aimed directly at the tumor. Chemotherapy drugs kill actively growing cancer cells, but sometimes cancer cells become resistant to chemotherapy (even when several drugs are used in combination). The plasma membrane in resistant cells contains a carrier that pumps toxic chemicals out of the cell. Researchers are testing drugs known to poison the pump in an effort to restore sensitivity to chemotherapy. Unfortunately, both chemotherapy and radiation kill normal cells as well as the cancer. The patient will suffer the negative side effects of therapy: nausea, vomiting, hair loss, weight loss, anemia, etc. Thus, the use of chemotherapy and radiation must be balanced carefully: strong enough to kill cancer, but not so strong as to cause the person's death. The What's New reading on page 80 describes emerging technologies that will specifically target cancer cells while sparing healthy cells. Individuals should be aware of the seven danger signals for cancer (Table 4A) and inform their doctor when any one of these are observed. Further, the evidence is clear that the risk of certain types of cancer can be reduced by lifestyle changes. For example, avoiding excessive sunlight reduces the risk of skin cancer, and abstaining from cigarettes, cigars, and chewing tobacco reduces the risk of oral, throat, and lung cancers, as well as other types of cancer. Exercise and a healthy diet are also believed to be important. Recommendations include: Lowering total fat intake Eating more high-fiber foods Increasing consumption of foods rich in vitamins A and C Reducing consumption of salt-cured and smoked foods Including vegetables of the cabbage family in the diet Consuming only moderate amounts of alcohol

menings

The meninges are membranes found within the posterior cavity (see Fig. 1.5). They are composed only of connective tissue and serve as a protective covering for the brain and spinal cord. Meningitis is a life-threatening infection of the meninges (see the Medical Focus on page 9).

Transitional Epithelium

The term transitional epithelium implies changeability, and this tissue changes in response to tension. It forms the lining of the urinary bladder, the ureters (tubes that carry urine from the kidneys to the bladder), and part of the urethra (the single tube that carries urine to the outside). All are structures that may need to stretch. When the walls of the bladder are relaxed, the transitional epithelium consists of several layers of cuboidal cells. When the bladder is distended because it is filled with urine, the epithelium stretches, and the outer cells take on a squamous appearance. It's interesting to observe that the cells in transitional epithelium of the bladder are physically able to slide in relation to one another, while at the same time forming a barrier that prevents any part of urine from diffusing into the internal environment.

The fibroblasts of reticular connective tissue

are called reticular cells, and the matrix contains only reticular fibers. This tissue, also called lymphatic tissue, is found in lymph nodes, the spleen, thymus, and red bone marrow. These organs are a part of the immune system because they store and/or produce white blood cells, particularly lymphocytes. All types of blood cells are produced in red bone marrow.

connective tissue

binds structures together, provides support and protection, fills spaces, produces blood cells, and stores fat. As a general rule, connective tissue cells are widely separated by a nonliving, extracellular matrix composed of an organic ground substance that contains fibers and varies in consistency from solid to semifluid to completely fluid. Whereas the functional and physical properties of epithelial tissues stem from their cells, connective tissue properties are largely derived from the characteristics of the matrix (Table 4.2).

Junctions

tight junction forms an impermeable barrier because adjacent plasma membrane proteins actually join, producing a zipperlike fastening (Fig. 4.17a). In the stomach, digestive secretions are contained, and in the kidneys, the urine stays within kidney tubules because epithelial cells are joined by tight junctions. A gap junction forms when two adjacent plasma membrane channels join (Fig. 4.17b). This lends strength, but it also allows ions, sugars, and small molecules to pass between the two cells. Gap junctions in heart and smooth muscle ensure synchronized contraction. In an adhesion junction (desmosome), the adjacent plasma membranes do not touch but are held together by extracellular filaments firmly attached to cytoplasmic plaques, composed of dense protein material (Fig. 4.17c). Desmosomes that join heart muscle cells prevent the cells from tearing apart during contraction. Similarly, desmosomes in the cervix, the opening to the uterus (womb), prevent the cervix from ripping when a woman gives birth.