During a lifetime, many of the cells that make up the body age and die. These cells must be replaced so that the body can continue functioning optimally. Reasons that cells are lost and must be replaced include the following:
- Sloughing off of epithelialA type of tissue (epithelium) that covers our exposed surfaces, such as skin. Also lines our hollow or tube-like organs/tissues such as the digestive tract. Since these tissues are often exposed to environmental insults such as chemicals and solar radiation and are often divide rapidly to replace lost cells, many cancers arise in epithelial tissues. cells such as those lining the skin and intestines. The old, worn out cells on the surface of the tissues are constantly replaced. A special case of this is the monthly replacement of the cells lining the uterus in pre-menopausal women.
- Wound healing requires that cells in the area of the damage multiply to replace those lost. Viral diseases such as hepatitis may also cause damage to organs that then need to replace lost cells.
- Replacement of the cells that make up blood. Red blood cells carry oxygen to tissues. White blood cells such as B and T lymphocytes are part of the body's immune system and help to ward off infections. Most of these cells have very short lifespans and must be constantly replaced. The precursors of these cells are located in bone marrow. These precursors, or stem cells, must reproduce at a very high rate to maintain adequate amounts of the blood cells.
The process by which a cell reproduces to create two identical copies of itself is known as mitosisThe portion of the cell cycle (M stage) during which a cell divides into two (usually identical) daughter cells.. The goal of mitosis is the formation of two identical cells from a single parent cell. The cells formed are known as daughter cells. In order for this to happen, the following must occur:
- The genetic material, the DNAAbbreviation for deoxyribonucleic acid. Composed of very long strings of nucleotides, which are abbreviated as A, C, G and T. DNA is the storage form of our genetic material. All of the instructions for the production of proteins are encoded in our DNA. in chromosomes, must be faithfully copied. This occurs via a process known as replicationThe process by which DNA is duplicated. DNA replication occurs during the S phase (synthesis) of the cell cycle. Many chemotherapy drugs act during DNA replication. Some are incorporated into the newly replicated DNA and cause problems. Others interfere with enzymes necessary for DNA replication. See topoisomerase..
- The organelles, such as mitochondria Mitochondria are subcellular organelles responsible for extracting the bulk of the energy we use from the food we eat. As a byproduct, oxygen radicals (reactive chemicals) are produced that may contribute to cancer formation by damaging DNA. A mitochondrion (the singular version of the word) is filled with inner membranes upon which the last stages of energy generation take place., must be distributed so that each daughter cell receives an adequate amount to function.
- The cytoplasmThe portion of a cell that is located outside the nucleus. This includes many organelles such as ribosomes and mitochondria. The cytoplasm also contains many fibers of the cytoskeleton. of the cell must be physically separated into two different cells.
As we will see, many of the features of cancer cells are due to defects in the genes that control cell division. The cell division process occurs as an orderly progression through four different stages. These four stages are collectively known as the cell cycle. Further information on the topics on this page can also be found in most introductory Biology textbooks, we recommend Campbell Biology, 11th edition.1 The following pages describe the cell cycle in detail.
Sections included on this page:
Normal Cell Division
There are several safeguards built into the cell division process to assure that cells do not divide unless they have completed the replication process correctly and that the environmental conditions in which the cells exist are favorable for cell division. Among others, there are systems to determine the following:
- Is the DNA fully replicated?
- Is the DNA damaged?
- Are there enough nutrients to support cell growth?
If these checks fail, normal cells will stop dividing until conditions are corrected. Cancer cells do not obey these rules and will continue to grow and divide.
Now that we have discussed the cell cycle, we will briefly address the ways in which cells are signaled to divide.
Most cells in the body are not actively dividing. They are performing their functions, such as the production of enzymes to digest food or helping to move the arms or legs. Only a small percentage of cells are actually going through the process just described.
Cells divide in response to external signals that 'tell' them to enter the cell cycle. These signals may take the form of estrogenA steroid sex hormone. Estrogen's structure is closely related to cholesterol. Produced by the ovaries, estrogen has effects on the reproductive, cardiovascular and skeletal systems. Estrogen is also a growth factor for some types of cells, including breast cells. Inhibitors of estrogen function such as tamoxifen and arimidex are used to block the growth effects of estrogen. See also, estrogen receptor. or proteins such as platelet derived growth factorA substance that stimulates cell division. Growth factors are usually small proteins or steroid hormones. They may be secreted by the same cells on which they act or by cells that reside in a different part of the body than the target cells. Some examples of growth factors include estrogen, a growth factor for breast cells, and VEGF, a growth factor that causes the development of blood vessels. Several different anti-cancer treatments are designed to inhibit the activity of growth factors. (PDGF). These signaling molecules, depicted as an X-shaped molecule in the animation below, bind to their target cells and send signals into the nucleusPlural, nuclei. A subcellular organelle that contains the chromosomes. Present in eukaryotic cells, the nucleus is surrounded by the nuclear envelope. Within the nucleus is a region called the nucleolus in which the parts of ribosomes are constructed. The nuclear pores allow for the import and export of materials.. The result is that the genes responsible for cell division are turned on and the cell divides. For example, a cut in the skin leads certain blood cells, platelets, to produce a growth factor (that causes the skin cells to reproduce and fill the wound. Cell division is a normal process that allows the replacement of dead cells.
Normal Cell Division II
What are the signals that make cells stop dividing?
A lack of positive external signals causes cells to stop dividing.
Contact inhibition
Cells are also able to sense their surroundings and respond to changes. For instance, if a cell senses that it is surrounded on all sides by other cells, it will stop dividing. In this way, cells will grow when needed but stop when their goal has been met. To revisit our wound example, the cells fill in the gap left by the wound but then they stop dividing when the gap has been sealed. Cancer cells do not exhibit contact inhibition. They grow even when they are surrounded by other cells causing a mass to form. The behavior of normal (top animation) and cancer cells (bottom animation) with regard to contact inhibition is depicted below.
The round containers in which the cells are depicted in the animations are called petri dishes. In the laboratory, cells are often grown in these, covered with a nutrient-rich liquid.
Cellular SenescenceIn the context of cell division, the term refers to the aging and death of a culture of cells. All normal cells (aside from stem cells) have a limited ability to divide. Cancer cells do not undergo senescence, instead, they are capable of dividing indefinitely. Cells which can divide indefinitely are termed immortal. Outside of cell biology, senescence refers to the aging process.
Most cells also seem to have a pre-programmed limit to the number of times that they can divide. Interestingly, the limit seems to be based, in part, on the cell's ability to maintain the integrity of its DNA. An enzymeA protein that speeds up the process of chemical reactions in the body without becoming altered in the process. Almost every biological process is driven by the activity of enzymes. Without enzyme catalysts, the complex reactions that build and break down cell parts would not happen at a rate compatible with life. Enzyme names usually describe the reaction that is being catalyzed and all of them end in -ase., telomeraseAn enzyme that functions to replace the ends of chromosomes. Normally, during DNA replication, chromosome ends are shortened by a small amount. Telomerase is turned off in most adult tissues, a process that limits the number of cell divisions that can be completed by those cells. In cancer cells, telomerase is often reactivated, allowing the cells to divide indefinitely., is responsible for upkeep of the ends of the chromosomes. In adults, most of our cells don't utilize telomerase so they eventually die. In cancer cells, telomerase is often active and allows the cells to continue to divide indefinitely. For more information on telomerase, see the Cancer Genes section
Cancer Cell Division
When it comes to cell division, cancer cells break just about all the rules!
- Cancer cells can divide without appropriate external signals.This is analogous to a car moving without having pressure applied to the gas pedal. An example would be the growth of a breast cancer cell without the need for estrogen, a normal growth factor. Some breast cancer cells actually lose the ability to respond to estrogen by turning off expression of the receptor for estrogen within the cell. These cells can still reproduce by bypassing the need for the external growth signal.
- Cancer cells do not exhibit contact inhibition.While most cells can tell if they are being 'crowded' by nearby cells, cancer cells no longer respond to this stop signal. As shown above, the continued growth leads to the piling up of the cells and the formation of a tumor mass.
- Cancer cells can divide without receiving the 'all clear' signal.While normal cells will stop division in the presence of genetic (DNA) damage, cancer cells will continue to divide. The results of this are 'daughter' cells that contain abnormal DNA or even abnormal numbers of chromosomes. These mutant cells are even more abnormal than the 'parent' cell. In this manner, cancer cells can evolve to become progressively more abnormal.
Continued cell division leads to the formation of tumors. The genetic instability that results from aberrant division contributes to the drug resistance seen in many cancers. Mutations in specific genes can alter the behavior of cells in a manner that leads to increased tumor growth or development.
More information on this topic may be found in Chapter 8 of The Biology of Cancer by Robert A. Weinberg.
Cell Division Summary
Cell Division Control
- Cell division is a normal process.
- Mechanisms exist to ensure DNA replication occurs correctly and the environmental conditions are favorable for cell division. Replication errors may also be corrected after they occur.
- Normal cells stop dividing when there is genetic damage or conditions are not favorable. Cancer cells continue to divide even when conditions are not appropriate.
Cell Division Signaling
- Most cells in the body are not actively dividing, but are carrying out their normal functions.
- Cells divide in response to external signals in the form of proteinOne of the four basic types of biomolecule. Proteins are polymers made up of strings of amino acids. Proteins serve many functions in organisms including transport of molecules, structure, cell adhesion and as signaling molecules such as hormones. Many transcription factors, including p53 and Rb are proteins. or steroidA type of lipid. Steroids are composed of four carbon rings fused to form one flat (planar) molecule. Examples of steroids include cholesterol, testosterone and estrogen. growth factors.
- Cells stop dividing for several reasons, including:
- A lack of positive external signals
- The cell senses that it is surrounded on all sides by other cells-contact dependent (density dependent) inhibition
- Most cells seem to have a pre-programmed limit of the number of times they can divide
Cell Division in Cancer Cells
- Cancer cells can divide without appropriate external signals.
- Cancer cells do no exhibit contact inhibition.
- Cancer cells continue dividing in the presence of genetic damage.
- The uninhibited, continued division of genetically damaged cells can lead to tumor formation.
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