Cancer and How It Develops

Cancer is characterized by the uncontrolled growth of cells, invasion of surrounding tissue and metastasis through which other locations in the body are affected. These characteristics differentiate a malignant tumor from a benign tumor which is an abnormal but localized tissue mass that can be surgically removed.
Genetic abnormalities accumulate in cancerous cells and exhibits changes in the cell shape, nuclei and organization. These cells can be distinguished by its unusually large and irregular nuclei. Such pre-cancerous cells proliferate uncontrollably on its way to malignancy. However a tumor on reaching a critical mass secretes chemicals to tempt blood vessels to invade the tumor to provide a channel for its nutrient supply and waste removal to support its uncontrolled growth. This also opens up a route for the cancer cells to metastasize or spread to other locations in the body through the blood and lymph vessels making surgical removal impossible. Chemotherapy or radiation is used to destroy metastasized cells.
Genes involved in cancer development
Cancerous cells defy the control mechanisms that are placed to regulate cell division. In a normal cell cycle proto oncogenes and tumor suppressor genes in combination with each other regulate cell division. Proto-oncogenes promote the division of cells through its effects on growth factors or by producing them where as products of tumor- suppressor genes act in damage control such as repair and programmed cell death. Mutations in these genes results in malfunctions in cell cycle and leads to uncontrolled cell division giving rise to cancerous cells. Mutation in the tumor-suppressor gene p53 is associated with more than half known cancers. A protein produced by gene p53 regulates another gene whose gene product keeps a check on cell division. A mutation in p53 lifts that check resulting in uncontrolled cell division. Mutations in a proto-oncogene turn it to an oncogene which produces larger amounts of proteins (which are mostly growth factors or its receptors) or enhances the activity of the protein resulting in hyper stimulation of cell-division.
Characteristics of cancer cells
A distinguishing character of cancer cells is its lack of contact inhibition. They are devoid of anchorage unlike in normal cells that stop division on contact with neighboring cells through information from signaling systems.
Failure to trigger the mechanism of programmed cell death or apoptosis also is a characteristic of cancerous cells. The genetic suicide program is activated in normal cells in response to a physiological or biological signal in case of faulty regulator genes. A mutation in the tumor-suppressor gene p53 is responsible partially for the failure of this mechanism in cancer cells as p53 also functions to prevent damaged DNA replication. The gene stops cell division for the damaged DNA to be repaired and initiate apoptosis when the damage is beyond repair. A mutated p53 fails to initiate the process and continue division and metastasis which is not even susceptible to radiation or chemotherapy which relies on programmed cell death to destroy the cancer cells by damaging its DNA.
Telomerase enzyme responsible for telomeres at chromosome tips serve as an indicator of the number of cell divisions as it is shaved off from the chromosome with every cell division until it is no more resulting in the death of the cell. Cancerous cells seem to have an unceasing telomerase production which might be the reason for its unlimited cell division.
Metastasis which occurs due to the formation of blood vessels in cancerous cells is due to the mutation in p53 as it also produces proteins that prevent the formation of blood vessels in tissues normally due to the damage it could cause to certain tissues.
Cellular adhesion molecules (CAMs) holding cells together are dissolved by enzymes secreted by cancerous cells that break loose and enter circulation to spread to different locations. It evades self destruction as would have happened in normal case on being unanchored by the false message send to the nucleus by its oncogenes saying the cells are properly anchored.
Defense cells in the body such as natural killer cells and cytotoxic T cells distinguish cancer cells from normal body cells by its altered membrane proteins and destroy them. However some cancer cells evade this mechanism by actively inhibiting the defense cells or actively multiplying without being destroyed by the defense cells.
A number of factors are implicated in the formation of cancer in addition to the heritable multiple mutations carried in genes. A physical factor or substance that transforms a normal cell into a cancerous cell is called a carcinogen. Some of the carcinogens are described below:
Microbial agents: Some viruses and bacteria contribute to less than 15% of known cancers. Viruses replicate by inserting its DNA into the host and might contribute to the development of cancer by impairing a normal gene function. Some of the cancer causing viruses include Human papillomavirus (cancers of the cervix and penis), Hepatitis B and hepatitis C viruses (liver cancer) and HIV(Kaposis sarcoma, non Hodgkin’s lymphoma).The bacterium Helicobacter pylori is implicated in stomach cancers.
Chemical agents: Chemical agents cause cancer by damaging DNA directly and also by increasing the potency of other carcinogens with its presence. Most of the chemical carcinogens are of industrial origin and include pesticides, dyes, asbestos, soot, coal tar, benzene and vinyl chloride.
Radiation: Skin cancer particularly that of the melanin producing cells called melanoma caused by the ultraviolet B rays in sun’s radiation is the most frequent and dangerous of cancers caused by radiations. Frequent sunburns as well as exposure to ultra violet radiations from tanning booths and sun lamps increase the risk of melanoma. Other sources of radiation are radioactive radon gas released by soil, rock and groundwater as well as trace amounts from household appliances, power lines and cellular phones.
Tobacco: Tobacco is considered the most lethal carcinogen in the United States accounting to over 30% of cancer deaths. Smoking raises the risk of cancers of the mouth, pharynx, lungs, pancreas and the bladder. Passive smokers are also at risk of lung cancer while chewing and snuffing tobacco is a risk factor of cancers of esophagus, pharynx and mouth.
Diet: Risk factors in diets include saturated animal fat and red meat that might cause cancers of prostate, colon and rectum whereas an increased salt intake might cause stomach cancer. Aflatoxin is a fungal carcinogen that infects nuts. Obesity is also considered a general risk factor for a number of cancers.
Internal factors: Free radicals produced by biochemical reactions in the body are detoxified by peroxisomes. Inefficient detoxification might result in its accumulation which might cause damage to molecules including DNA. The contribution of these free radicals to the development of cancer is still under study.
Cancer development is a multi step process with a number of risk factors and gene mutations implicated in the process. The hereditary predisposition to the disease depends upon the number of genes damaged. At least two gene mutations and in most cases more than six gene mutations are required for a cancer to develop.
REFERENCES
Goodenough, J..McGuire, B, (2010) Biology of humans: concepts, applications, and issues, 3rd ed. San Francisco, CA: Pearson Benjamin Cummings: 470-476
Johnson, M.D. (2010) Human biology: concepts and current issues, 5th ed. San Francisco: Pearson Benjamin Cummings: 426-428