Cell Cycle and Cancer
Cell Cycle and Cancer: Introduction
Multi-cellular organisms are made up of millions of tiny cells. In any one organism, there are many different types of cells. Cells that share a common structure and function can be found grouped and organized into tissues. There are four basic types of animal tissue: epithelial, muscle, nerve, and connective tissue.
The cells of epithelial tissues pack tightly and form the lining of many parts of the body, for example in the intestine as shown below. The cross-section of the intestine shows that it is covered by villi that greatly increase the surface area for absorption of nutrients from the lumen (inside of the intestine). The micrograph at the lower right shows the epithelial cells that line the inside of the intestine. If you click on the illustration below you will see an enlargement of the micrograph. If you look carefully, you may even see that the surface of each epithelial cell that lines the intestine is covered with hundreds of finger-like projections called microvilli. The microvilli increase the absorptive area of the epithelial cell lining greatly.
In addition to the intestinal lining, epithelial cells form sheets of cells in other tissues such as the lining of the lungs, bladder, kidneys, blood vessels, and other tissues as well.
Muscle tissue contains special cells that can contract because they have long protein fibers that can slide past each other and generate force.
As shown in the illustration above (click on image to enlarge), there are several different types of muscle in the body. The muscle most students think of first is skeletal muscle. These are the muscles that allow us to move our limbs, head, and other parts of the body that we can voluntarily move. The insert in the upper right of the illustration shows how highly organized skeletal muscle is. Smooth muscle causes movement in organs of the body that we typically cannot voluntarily control (involuntary muscle). These include much of the digestive system and blood vessels. Sometimes when you hear sounds from your abdomen, you are hearing the gas and other material being moved along the digestive tract by the slow contraction of smooth muscles. Smooth muscle is not as highly organized at the tissue level as skeletal muscle but uses similar proteins to generate force.
Finally, there is cardiac muscle. Cardiac muscle is not quite as organized as skeletal muscle but, like smooth muscle, uses many of the same proteins to generate force. The amazing feature of cardiac muscle cells (cardiomyocytes) is the regularity and synchrony of their contraction. The beating cardiomyocyte shown here is in a tissue culture dish. It was filmed in the lab of Ben Prosser, Ph.D., Perelman School of Medicine, University of Pennsylvania. Even in isolation cardiac muscle cells demonstrate the ability to contract with a regular beat. In the heart, millions of these cells coordinate to beat in unison, pumping blood throughout the body. On an average day, your heart beats about 100,000 times. That’s over 4,000 times per hour or about 70 times per minute. You can confirm this by taking your pulse on your wrist. Just count how many beats you count in 60 seconds.
Nerve tissue contains long cells that can generate electrical signals in the body. There are a number of different types of cells in the nervous system. The average human brain contains about 100 billion (100,000,000,000) neurons. In addition, it contains somewhere between 10- and 50-times more additional cells that support the neurons. Neurons come in many different sizes, depending on their locations and functions. Some neurons in the human body are very small, well under a millimeter in length. On the other hand, some neurons in the human body are nearly a meter long!
The brain is an amazing and extremely active organ. Typically the brain represents only about 2% of the body’s total mass. On the other hand, it uses about 20% of all the energy consumed by the body. Awake or asleep, the brain demands a great deal of energy.
Connective tissue adds support and structure to the body. It can be found almost everywhere in the body including skin, bones, tendons, joints, ligaments, blood vessels, and bone. There are other, less common tissue types including adipose or fat tissue that have connective tissue as structural support.
Collagen, a large, fibrous molecule, makes up to nearly a third of the protein in the body. As shown in the illustration above, it is a component of the dermis layer of skin. Collagen helps the skin maintain its elasticity and tightness. As we age, collagen protein is damaged and lost. As a result, the skin loses its supporting structure, and wrinkles form.
Finally, you may be surprised to know that blood is considered connective tissue. It seems odd that a fluid like blood would be considered connective tissue since connective tissue is associated more with solid structure and support. However, when there is damage to a blood vessel, a scrape or cut, for example, the fluid in which the blood cells float, plasma, quickly forms a solid blood clot (click on the image to enlarge). This is because the blood plasma is richly concentrated with proteins, some of which form long, rope-like fibers to entrap blood cells and other circulating cells to prevent blood from escaping from the circulatory system. Without blood’s clotting ability, even a small cut could cause substantial blood loss. The illustration below depicts the formation of a blood clot in a vessel. Notice the thin fibers of protein that hold the blood cells together in the clot.
Tissues to Organs
Two or more tissues work together to form organs. An organ is a group of tissues that work together to perform a specific set of functions for the organism. There are many different organs throughout the human body. The lung, heart, liver, breast, and skin are just a few of the organs that maintain our bodies. In this CELL, you will learn about how the organization of cells within a tissue can determine the function of that tissue. You will have the opportunity to examine three tissue sections in the lab – human skin, lung, and breast.
Skin: The skin is an organ that contains several types of tissues including connective, epithelial, nerve, and muscle tissue. It is the largest organ in the human body! The function of this organ is to protect the body from external harm like the sun, heat, cold, and germs. As shown in the drawing below (click drawing to enlarge), the skin is composed of the epidermis, dermis, and subcutaneous layers. The epidermis is the outermost layer and it contains several cell types including epidermal and connective tissue cells. It also contains the pigment-producing cells called melanocytes. The pigment produced by these cells is called melanin.
The dermis layer of skin contains primarily connective tissue and muscle tissue. The muscle cells contract to make your hair stand up when you are frightened or cold! Finally, the subcutaneous layer contains adipose cells or fat cells. These cells are important because they are like a layer of insulation to keep us warm. This layer of the skin also contains the sweat glands and hair papilla. The hair papilla are the “root” or place where your hair grows from. Each layer of skin – epidermis, dermis, and subcutaneous – helps contribute to the overall function of the skin, to protect us from harmful UV light, heat, and cold.
Lung: As shown in the drawing below (click on drawing to enlarge), the lung mostly contains epithelial and connective tissues. The function of the lung is to allow the exchange of oxygen from the air we breathe to blood so that it can be delivered to other tissues in the body where it is needed for normal cell function. It also allows carbon dioxide waste in the blood that came from the tissues throughout the body to leave the body through exhalation.
Air enters the body when we breathe through the nose and mouth. The air travels down the trachea (windpipe) and into the bronchioles. There are bronchioles for the left and right lung lobe. The bronchioles lead to the terminal bronchioles and then the respiratory bronchioles that terminate in the alveolar ducts. The alveolar ducts are passageways that lead directly to the pulmonary alveoli which are small air sacs where the oxygen in the air is absorbed. These alveoli are composed of balloon-like structures with the walls of the balloon being made of a single layer of epithelial cells.
These epithelial cells are surrounded by tiny blood vessels called capillaries. The single-cell layer and tiny blood vessels allow for a very short distance for the oxygen in the air to travel into the blood and for the carbon dioxide in the blood to travel out into the air.
Breast: The breast is made of a combination of fatty (adipose), glandular, and connective tissue, as can be seen in the drawing here (click on the drawing to enlarge). These tissues function to supply milk for growing infants. Glandular tissues produces and releases substances for use in the body. In the breast, glandular tissue contains lobes that store the milk and ducts that transport the milk from the lobes to the nipple. During the majority of a woman’s life, the breast is inactive and does not produce milk. Milk production only occurs when the tissues become active some 3-5 days after a woman gives birth to a child. When the tissues become active, the lobules fill with milk and grow larger, the ducts expand and fat or adipose cells become smaller. This transition from inactive to active tissue requires large increases in the number of cells lining the lobules and ducts within the breast tissue. In the lab, when you examine active breast tissue, you will see large open areas (the lobes and ducts) where the milk is stored. Inactive tissue does not have as many large open areas because it is not storing milk, the lobes and ducts are smaller.
Cell Division Throughout Life
All of the tissues we have discussed require increases in cell number throughout the life of the human body. The skin has constant cell loss due to exposure to UV light from the sun and various other external damage. The lung alveoli cells are repeatedly exposed to damaging chemicals inhaled with the air in our environment including pollution and cigarette smoke. This damage causes cell death of the cells lining the alveoli and therefore requires replenishment of these cells. The breast must transform from the inactive tissue to the active tissue within days after a woman gives birth. This transition requires the production of many new cells lining the breast ducts and lobes.
The increased numbers of cells are supplied through increased cell replication (or cell division). Cell division must be closely regulated so that cells only divide when needed or the organization of these tissues would be destroyed making it impossible for them to function properly.
Cell division is also extremely important in early childhood. During this time of development, the human body grows at a very fast rate. For example, a baby may easily triple its birth weight in its first year. Relatively rapid growth continues into adolescence. This is due to a constant increase in the total number of cells making up the body.
Cell division is the process by which two identical cells are produced from a single parent cell. This process requires that the original (parent) cell copies all of its contents, including DNA and organelles, and splits these materials evenly into two new (daughter) cells. In this way, the cell makes an exact copy of itself and the number of total cells is increased.
Once an adult human is fully grown, most cells either stop or slow down this process of dividing. However, in certain tissues, like the skin, lung, or active breast tissue, cell division is still needed. Whether cell division is occurring rapidly as in a growing child, or at a slower rate as in certain adult tissues, this process must be carefully controlled. Too much or too little cell division interferes with normal tissue function. The process that controls cell division is called the cell cycle.
The Cell Cycle
The cell cycle is an ordered set of events that results in cell division – the production of two identical cells from a single parent cell. The cell cycle can be broken down into 4 distinct phases:
1. G1 or GAP phase
2. S or DNA synthesis phase
3. G2 or GAP2 phase
4. M or Mitosis phase
G1 Phase: During the G1 phase, the cell produces proteins and grows in size. During this phase, the cell is functioning normally, constantly making proteins. This constant increase in proteins is what causes the cell to get larger. The G1 phase ends when the cell has reached a certain size. Then, the S phase, or DNA synthesis phase, begins.
S Phase: During the S phase the cell will make an exact copy of the DNA contained in the cell nucleus through DNA replication. At the end of the S phase, each chromosome inside the nucleus of the cell consists of 2 identical sister chromatids. Each chromatid is made up of a double stranded DNA molecule.
G2 Phase: Next, the G2 or GAP 2 phase occurs. During this phase the cell has very little activity. The cell is no longer changing in size and is doing minimal metabolic activity.
M Phase: Finally, the M phase, or Mitosis phase, occurs. During this phase, the sister chromatids produced in the S phase are separated and cell division (cytokinesis) occurs. The M phase of the cell cycle is made up of four distinct stages or steps. We call this four-step process mitosis. The result of mitosis is two identical daughter cells from a single parent cell. The two daughter cells will then each enter a G1 phase of their own, producing two identical copies of themselves. This four-step process of mitosis is capable of many rounds of cell division.
The M phase or Mitosis phase of the cell cycle is made up of four distinct stages. When a cell is not in one of these stages it is said to be in interphase. Thus, cells that are leaving the G2 phase are in interphase. The mitotic steps after interphase are shown below (click on the illustration to enlarge).
The drawing of each of the steps in mitosis shown above is accompanied by a micrograph (photograph taken with a microscope). You will have the opportunity in the lab to examine microscope slides that display each other the mitotic stages. Pay particular attention to what is happening to the chromosomes at each step (you will see the chromosome much better here by clicking on the illustration above). Remember, the aim of mitosis is for a parent cell to replicate the DNA in its chromosomes so that two genetically identical daughter cells can be formed. Therefore, at the end of mitosis, two functional cells that are exactly the same will have replaced the single parent cell that entered mitosis from the G2 phase.
Prophase: Mitosis begins with prophase. In prophase, the chromosomes, which each contain sister chromatids produced in the S phase of the cell cycle, condense in the nucleus of the cell. At this stage, the nuclear membrane dissolves, and centrioles begin to form spindle fibers. Spindle fibers are thread-like protein structures that grow from the centrioles. Eventually, they will connect to the chromosome pairs during the metaphase and anaphase steps of mitosis.
Metaphase: During metaphase, the duplicated chromosomes line up at the midline of the cell in preparation for cell division. The spindle fibers attach to a unique area of each of the chromosome pairs called the kinetochore.
Anaphase: During anaphase, the sister chromatids separate from each other and move with the spindle fibers to opposite ends of the cell where each of the two centrioles are located. At this point, the genetic information from the parent cell is located at two opposite regions of the cell.
Telophase: Finally, during telophase, the chromatids have moved to the ends of the spindle fibers. The spindle fibers disappear and new nuclear membranes form around each set of chromosomes. At this point, the cytoplasm splits in half and cell division (cytokinesis) occurs.
The length of time for a cell to complete one full cell cycle (from one phase of mitosis to the next) varies depending on cell type. For example, a cell in an embryo may go through one round of the cell cycle in 1 hour while a cell in some adult tissues may take 1 year. The length of time of the full cycle varies primarily in the G1 (GAP1) phase. Cells can stay in the G1 phase for up to 1 year.
Cell Cycle Control
How does a cell “know” when to move between the phases of the cell cycle? Control of the cell cycle occurs through specialized proteins that are translated from specific genes in the cells DNA. When the cell makes these proteins, they allow the cell to transition into the next phase of the cell cycle. These proteins thus induce or turn on the cell cycle. There are also genes that code for proteins that block the cell from moving into the next phase of the cell cycle. These proteins inhibit or stop the cell cycle. It is the balance of these cell cycle inducing and inhibiting proteins that control the cell cycle.
Different cell types have different amounts of cell cycle control proteins and therefore different lengths of time that they will stay in each phase of the cell cycle. As we said, the majority of cells spend most of the time in the G1 phase before quickly moving through the other phases. In some rapidly dividing cells, the G2 phase only lasts a few minutes. For example, embryonic cells must rapidly divide to provide all the cells for the various developing organs. These cells have a very short G2 phase and rapidly move throughout the other phases of the cell cycle. In contrast, adult cells it may take 1 year for the cell to move from the G1 into the S phase and another month to go from G2 to the M phase.
Regulation of the cell cycle is very important. If cells divided at random, the organization of the tissue would be lost and the function of the organ would be affected. The proteins that control the cell cycle are produced when stimulated by external factors. For example, some cells, like the lung alveolar cells, must only grow in a single layer. When these cells come into contact with one another, interactions between the cell membranes stop the production of the proteins that force the cell into the cell division phase. When cell-cell contact prevents further cell division, it is called contact inhibition. In this way, the alveolar cells will only divide when they are not in contact with other cells. For example, when there is a hole in the alveolar wall or other damage to the tissue.
If the gene that codes for the controlling protein is damaged or mutated, then a properly functioning protein cannot be produced. If there is no production of the controlling proteins, the cells will go through the cell cycle and divide unregulated. Each new (daughter) cell will inherit the mutated gene for this controlling protein because the cell receives an exact copy of the DNA in the original (parent) cell. This means that every daughter cell produced from the originally damaged cell will also divide continuously. As you might imagine, such uncontrolled and often rapid cycles of cell division, or the lack of cellular control of the cell cycle, may lead to tumor formation and cancer.
Cancer Treatment: A Scientific Challenge
According to the National Cancer Institute, in 2020 an estimated 1,806,590 new cases of cancer will be diagnosed in the United States and 606,520 people will die from the disease. Among the most common cancers, in descending order of occurrence include breast cancer, lung cancer, prostate cancer, colon (intestinal) cancer, skin cancer, kidney cancer, uterine (uterus) cancer, leukemia, pancreatic cancer, thyroid cancer, and liver cancer. Approximately 39.5% of men and women in the United States will be diagnosed with cancer at some point in their lives.
On the positive side, as of January 2019, there were an estimated 16.9 million cancer survivors in the United States, and that number is predicted to rise to at least 22.2 million by 2030! That is, a diagnosis of cancer is by no means a death sentence. This, in turn, is because of early diagnosis and treatment of the disease. For example, the survival rate for leukemia has more than quadrupled in your parents’ lifetime. Perhaps you will someday join in the research and treatment of cancer and finally cure the disease completely. If you do, one thing is certain – you will take many more science and math courses!
Cancer is defined as a group of diseases that involve the uncontrolled cell division of body cells. Cancer begins when one normal body cell breaks free from normal controls of the cell cycle and begins to follow its own rate of cell division. This happens after damage to the cell’s DNA has occurred, which affects the production of a cell cycle controlling protein. All cells produced by this cell, and all cells from those daughter cells, will also follow an uncontrolled rate of cell division. This is because they all contain the same DNA as the result of mitosis.
If this process continues a tumor, a mass of cells, will develop. A tumor can invade normal tissue and therefore alter its overall organization and structure. This disorganization leads to an inability of the tissue to function, which in turn means that the organ cannot function properly.
If a single cancerous cell breaks away from the tumor it can travel in the blood to other places throughout the body. At a new site, this single cancer cell can proliferate and form another tumor. This type of spreading of cancer cells from one place in a patient’s body to another is called metastasis. You can read more about metastasis in the right-hand column of this page.
As mentioned above, lung cancer, also sometimes called adenocarcinoma, is one of the leading causes of death in adults. One of the primary causes of lung cancer is cigarette smoke. The chemicals in cigarette smoke are inhaled and absorbed by cells in the lung. Often when looking under the microscope at a lung tissue section from a smoker, deposits of tar (toxins) can be seen in the cells as small black specks. These toxins damage DNA. If the damage occurs on a gene that normally codes for a cell cycle controlling protein, cancer can develop.
Since cigarette smoke toxins damage DNA randomly, some people can smoke for many years and not develop cancer, while others may only smoke a few times and even quit and still get cancer. Even second-hand cigarette smoke (smoke from other people smoking) can cause damage to cells’ DNA. Lung cancer is not only caused by smoking, but this is thought to be one of the leading and preventable causes of lung cancer. You will examine microscope slides of human adenocarcinoma and compare them to normal human lung tissue in the lab.
Breast cancer develops when a normal duct or lobule cell transforms into a cancerous cell that divides in an uncontrolled manner. This transformation may happen after a mutation occurs in the gene that controls the production of a cell cycle controlling protein. Unlike lung cells, breast cells are not exposed directly to external factors. This means that this transformation occurs when there is a random mutation in one of these genes. This most likely occurs during normal DNA replication. Some mutations in DNA can be inherited. These inherited mutations often do not directly cause cancer to develop but puts a person at a higher risk to develop mutations that do cause cancer.
In the general population, 1 in 500 to 1,000 people have a mutation in the BRCA1 gene, which increases their risk of developing breast cancer. Therefore, individuals inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer. Today, if breast cancer is diagnosed early, many patients can be successfully treated with chemotherapy. Chemotherapy is when a cancer patient is given a medication that will stop cancer cells from dividing.
Traditionally, the three major forms of cancer treatment are surgery, radiation therapy, and chemotherapy. If a tumor can be easily removed surgically, this is often the first choice. However, some tumors are located in places that are difficult to remove without causing serious side effects. Also, if a tumor has metastasized and spread to diverse locations within the body, surgery may not be a reasonable choice.
Radiation therapy uses high doses of radiation to kill cancer cells. Sometimes this radiation can be applied from outside the body and sometimes it performed in combination with surgery. Interestingly, the mechanism that high doses of radiation kill cancer cells is similar to how normal cells are transformed into cancer cells in the first place – by damaging the cell’s DNA. Once tumor cells have sustained enough radiation damage they will die.
Chemotherapy can destroy tumors and cancer cells without surgery and radiation or in combination with these other treatments. With chemotherapy, the mechanism by which cancer cells are killed varies on the chemotherapeutic drug used. Some chemotherapeutic agents specifically kill cells that are actively dividing. Since cancer cells divide so frequently compared to most other body cells, such drugs can be highly effective. Other chemotherapeutic drugs focus on preventing cells from moving and thus metastasizing to other parts of the body.
Above, we discussed the three traditional means of cancer therapy. However, major advances in cancer research have provided new and useful approaches that promise to help many patients. Some of these treatments include the following:
Immunotherapy: Immunotherapy helps the immune system to fight cancer. The immune system normally functions to kill infections in the body caused by foreign agents like bacteria. Killing cancer cells by immunotherapy does not involve surgery or high doses of radiation.
Hormone Therapy: Some cancer cells require the body’s hormones in order to divide and grow. Hormone therapy is used to slow down or stop these types of cancer cells from dividing, particularly breast and prostate cancers.
Stem Cell Transplant: Radiation therapy may damage normal cells as well as cancer cells. Blood cells are made from very rapidly dividing cells so they can become damaged during radiation treatment for cancer. Stem cell transplants do not directly kill cancer cells, but rather increase the production of blood cells. Thus, this type of therapy can be used along with other cancer treatments.
In addition to those mentioned above, there are new and exciting forms of cancer treatment being developed all of the time. In fact, the more we learn about the biology, chemistry, and physics of normal and cancer cells, the more innovative new cancer treatments will be developed. By the time students doing this LabLearner CELL today grow up, there will likely be more effective ways of treating cancer. In fact, many of the cancer researchers that will make the greatest advances in cancer treatment in the future may well be in middle school today.
- Interesting Facts
- Learn the Lingo
- Get Focused
Metastasis: Why it’s called Cancer
You may wonder why the name cancer is used to describe this disease. The term dates back to ancient Greek and Roman times. The word cancer is the Roman term for crab. You may also know that Cancer is one of the Zodiac signs because ancient astrologers thought that the star-group constellation looked like a crab. Even though astrology (as opposed to astronomy, which is an authentic modern field of science) and zodiac signs are far from scientific, the name has stuck until this day. Nonetheless, looking at the animation of cancer cells spreading from a tumor and into surrounding tissue does have a crab-like appearance.
The spreading of cancer cells from a tumor is called metastasis. Metastasis involves both uncontrolled cell division and cell motility or cell migration. As you might suppose, tumors that are nonmetastatic, that is they do not display the ability to spread into surrounding tissue, are much less dangerous than metastatic tumors.
Join the Fight
Cancer is becoming better understood because of the many men and women who have dedicated their lives to fighting it. You may want to join the fight when you are grown. If you decide to, here are just some of the professions that you may end up choosing.
Partial list of cancer professions:
- Cancer Research Scientist (requires doctorate degree, Ph.D.)
- Cell Biologist
- Laboratory Technician (requires bachelors/masters degree)
- Physician (Requires medical degree, M.D.)
- Medical Technician (requires bachelors degree/specific technical training)
- Patient care professionals (requires bachelors/masters degree)
- Nurse Practioner (requires bachelor degree/grad school)
- Registered nurse (bachelor degree, R.N.)
- Doctor of Nursing Practice (doctorate, DNP)
It is important for you to note that all of the degrees and professions listed above as well as many, many more not included on this list, require science-related college degrees. You should also know, and this is important, that what you are learning in science and math in school right now is an essential part of the process!
LEARN THE LABLEARNER LINGO
The following list includes Key Terms that are introduced within the Backgrounds of the CELL. These terms should be used, as appropriate, by teachers and students during everyday classroom discourse.
Note: Additional words may be bolded within the Background(s). These words are not Key Terms and are strictly emphasized for exposure at this time.
- Tissue: a group of organized cells that share a common structure and function
- Organ: a group of tissues that work together to perform a specific set of functions for the organism
- Cell division: the production of two identical cells from a single parent cell
- Cell cycle: an ordered set of events that results in cell division
- Mitosis: M phase; the final phase of the cell cycle in which the sister chromatids produced in the S phase are separated and cell division (cytokinesis) occurs
- Chromosome: a structures in the nucleus of a cell containing two chromatids
- Chromatid: one double-stranded DNA molecule complexed with protein
- Cancer: a group of diseases that involve the uncontrolled cell division of body cells
- Metastasis: When a single cancerous cell breaks away from a tumor and it travels in the blood to other places throughout the body. At the new site, this single cancer cell can proliferate and form another tumor.
- Adenocarcinoma: a form of lung cancer
The Focus Questions in each Investigation are designed to help teachers and students focus on the important concepts. By the end of the CELL, students should be able to answer the following questions:
- How does the organization of cells within an organ relate to an organ’s function?
- How do cells in an organism replenish themselves after normal wear and tear to the tissue?
- How do tissues replenish the cells contained within them?
- What controls the process of cell division?
- What is the relationship between the control of the cell cycle and cancer?