What are tumors?
Tumors, also called neoplasms, are caused by a variety of factors—including mutations, improper hormonal signaling, viruses, and environmental influences—which cause certain normal body cells to deviate from a genetically determined developmental pattern for that particular organism. Tumors arise in all multicellular eukaryotic organisms, such as animals, plants, and fungi, where colonies of cells are intricately connected and are dependent on one another.
A tumor arises when a mistake is made in the cellular expression of a given gene. At a certain point in the cell’s development, a gene may be activated when it should not produce protein, or it may be inactivated when it should be producing protein. In either case, a cascade of subsequent developmental changes within the cell may be initiated. The cell may function inefficiently, die, or start to grow and divide at a faster rate than normal. In this latter scenario, the cell has become tumorous.
Many developmental biologists view the tumorous state as a throwback to the early embryonic development of the organism, when cells are undifferentiated and do not reveal the effects of specific hormonal genetic controls. Therefore, tumors reflect a dedifferentiated state of the cell. Tumors may be benign or malignant. A benign tumor grows as an enlarged tissue region without spreading elsewhere; often, it is only an inconvenience or irritant to the organism without harming the individual. A malignant tumor is invasive, spreading rapidly throughout many tissues, draining the organism of various resources, and eventually destroying key tissues and killing the individual. The breaking off and rapid spread of malignant tumors is termed metastasis.
The changes within genes and the subsequent gene expression or cellular dedifferentiation associated with tumors are brought about by mutations, changes within the nucleotide sequence (the genetic code) of the genes. Mutations can be caused by a number of agents called mutagens. Two major classes of mutagens are chemical mutagens (including benzene, carbon tetrachloride, and diethylstilbestrol) and radiation such as ultraviolet light, X radiation, and gamma radiation. Some mutagens also are carcinogens, causing malignant tumors. Not all mutagens, however, are also carcinogens. Caffeine, for example, is mutagenic but not carcinogenic.
Tumors can arise within cells of any of the five principal tissue types: epithelia, endothelia, connective tissue, nerve, and muscle. Epithelial tissue lines the organs outside and inside the body, including the skin, exocrine glands (such as oil and sweat glands), the digestive tract, and the reproductive organs. Endothelial tissue includes blood cells, blood vessels, and lymph nodes and glands. Connective tissue includes bone, fat cells, and cartilage. Nerve tissue includes the billions of nerves that compose the brain, spinal cord, and peripheral sensory and motor nerves. Muscle tissue includes the heart, more than six hundred skeletal muscles, and tens of thousands of smooth muscles.
Epithelial tissue cancers collectively are called carcinomas; they include adenocarcinomas, basal cell carcinomas, melanomas, malignant melanomas, squamous cell carcinomas, cervical cancer, uterine cancer, prostate cancer, colorectal cancer, and lung cancer. Whereas benign tumors of the skin such as freckles, moles, and warts are not serious, cancers of the skin and internal organ membranes can be fatal. Adenocarcinomas affect glands. Basal cell carcinomas, melanomas, and squamous cell carcinomas are serious cancers of the skin that can arise from prolonged sun exposure. Malignant melanoma is a rapidly invasive skin cancer that can penetrate other body tissues and cause death within two or three months. Cervical and uterine cancers are serious tumors of the female reproductive tract. Prostate cancer is prevalent among males and is a leading cause of cancer deaths. Colon and rectal cancers, believed to be triggered by the lack of roughage in diets, are also relatively common. Lung cancer may result from exposure of lung tissue to cigarette smoke and air pollution.
Endothelial tissue cancers include leukemias, which affect blood cells, and lymphomas, which affect lymphatic tissue. Most leukemias affect the immune system’s white blood cells (leukocytes) or the stem cells from which they are derived. Leukemias include acute lymphoblastic leukemia, acute myeloblastic leukemia, acute monoblastic leukemia, chronic lymphocytic leukemia, and chronic granulocytic leukemia. Lymphatic cancers attack the lymph nodes and glands that serve as blood reservoirs for the circulatory system. Lymphatic cancers include lymphosarcomas, Hodgkin disease, and Burkitt lymphoma, which is induced by the Epstein-Barr virus.
Connective tissue tumors include benign varieties such as osteomas and osteochondromas affecting bone, chondromas affecting cartilage, and lipomas affecting adipose (fat) tissue. Connective tissue cancers are called sarcomas. Chondrosarcomas are cartilaginous tissue cancers affecting joints. Osteosarcomas are bone cancers. Liposarcomas are fatty tissue cancers that attack a variety of bodily regions. Fibrosarcomas are cancers of the dense, fibrous tissue that holds together many bodily structures, including the skin.
Benign muscle tissue tumors are called myomas, whereas malignant muscle cancers are called myosarcomas. Leiomyosarcoma is a malignancy of smooth, visceral muscle. Rhabdomyosarcoma is a malignancy of cardiac and skeletal muscle.
Benign tumors of the central nervous system are called neuromas and neurofibromas. They include multiple neurofibroma, a condition in which numerous nerve tumors develop throughout the body, thereby causing a severely distorted physical appearance; multiple neurofibroma (or neurofibromatosis) is also known as the “Elephant Man” syndrome after the term used to describe Joseph Merrick, a nineteenth-century Englishman who suffered from this disease. Nervous system cancers include brain cancer and neurogenic sarcoma, glioblastoma, neuroblastoma, and malignant meningioma.
The formation of tumors is probably triggered by many factors. For example, the stress associated with living in a fast-paced technological society causes severe disturbances to the normal homeostatic balance within the body, particularly with reference to the nervous and endocrine systems. The nervous system activates many organ systems and tissues throughout the body. Even more potent in its effects is the endocrine system, which directly controls gene expression in various body cells and tissues via chemical messengers called hormones. When these hormones are hyperactivated by stress, they may activate or inactivate certain genes and their protein products at the wrong time in an individual’s development, thereby causing drastic changes in cellular functioning, often accompanied by abnormal growth of tissue into a tumor.
Virus infections may also result in cancer. In 1908, cell-free extracts prepared from leukemia in mice were shown to transmit the disease. In 1910, Peyton Rous discovered that a similar filterable agent would transmit a solid tumor, a sarcoma, in chickens. However, it was felt at the time that cancers in animals represented special circumstances, and that the work was not directly applicable to human cancer. The existence of the Rous sarcoma virus (RSV) was corroborated later by other researchers, culminating in the awarding of the 1966 Nobel Prize in Physiology and Medicine to Rous. Most human cancers are of endogenous (genetic) origin and not associated with viral infection, but there are a number of notable exceptions. Hepatitis B virus infection is associated with a hepatocarcinoma, or cancer of the liver. The Epstein-Barr virus, the etiological agent of infectious mononucleosis, is associated with both Burkitt lymphoma and nasopharyngeal carcinoma.
Oncologists and other medical researchers study both benign and malignant tumors. Studies are devoted to the occurrence of these tumors, improved means of diagnosis, and the development of effective treatments. Cancer is the second-leading cause of death in many Western nations. Stress, viruses, pollution, and an individual’s everyday exposure to hazardous materials increase the chance of developing tumors.
Regardless of a tumor’s cause, it is important that it be identified and treated. The American Cancer Society’s seven warning signs for cancer serve as an important model for tumor and cancer prevention. The warning signs are a sore that does not heal, persistent coughing, a lump anywhere on the body, unusual bleeding, a change in a wart or mole, a change in bladder or bowel movements, and difficulty swallowing.
Tumors may be benign or malignant. Benign tumors are less severe in most cases because they continue to grow within a localized region without invading other tissue regions. Benign tumors may press on critical organs and cause discomfort, however, thereby necessitating their surgical removal or inactivation using lasers, freezing, cytotoxic chemicals, or radiation. Warts represent a good example of a benign tumor. Warts are caused by a papillomavirus that infects skin cells of the dermis and enters a lysogenic phase, where it lays dormant in the host cell DNA but accelerates cell growth into a small tumor. A person can contract a papillomavirus merely by shaking an infected individual’s hand. Some warts may become malignant.
Malignant tumors are invasive cancers that multiply rapidly, break off into the bloodstream, and colonize other body regions, where they destroy tissues, organs, and sometimes the entire organism. Malignant cancer cells are immortal in the sense that they reproduce without any developmental barriers. Many malignant colonies can manipulate available blood supplies away from normal tissue, thereby promoting their own growth. Malignant cancers are classified according to tissue type. Any tissue is subject to cancerous growth, given the appropriate stimuli.
Genetic and biochemical research focuses heavily on the study of neoplastic cellular transformation. The prime emphasis is upon gene regulation, the ultimate control point that determines whether a cell will function properly. Mutations in gene regulatory regions, improper hormonal signaling, or viral interference via lysogeny may contribute to abnormalities in cellular growth.
Benign and malignant tumors can be induced and studied in laboratory animals. The application of a chemical mutagen to a localized tissue region in a mouse usually gives rise to a tumor. Female mice infected with the mouse mammary tumor virus pass the virus to their young via milk during suckling; this virus generates grotesquely large tumors that are often as big as the mouse itself. Tumors or sections of tumors removed from humans are studied by biopsy and subsequent biochemical analysis. Human cells are grown in tissue culture in flasks and roller bottles containing fetal calf serum so that medical researchers can study the nature of the neoplastic tumorous cells.
The study of tumors is of critical importance to medicine because tumor formation is a major cause of illness in millions of people yearly. An understanding of the genetic mechanisms underlying tumor formation is directly applicable to both the study of cancer and the understanding of mechanisms that regulate cell growth in general.
Critical to understanding the genetic basis of cancer was the discovery of retroviruses, RNA viruses that replicate using a DNA intermediate. These viruses were discovered to carry oncogenes, cancer-causing genes that the viruses originally acquired from the cells they infected. It was discovered that oncogenes actually encode a variety of proteins that regulate cell growth, including growth factors and DNA regulatory proteins. The genetic basis behind most human cancers seems to involve mutations in these genes. The study of the mechanism by which these proteins function may eventually lead to a fuller understanding of how cancers develop.
Since most cancers have a genetic origin, the ability to screen for certain genetic patterns allows clinicians to observe patients most at risk for the disease. For example, women who carry certain forms of the genes BRCA1 and BRCA2 are at greater risk for developing ovarian or breast cancer.
Developing cancers in certain tissues may also secrete unique forms of proteins, allowing for detection of the disease at an early stage. For example, prostate tumors, the leading form of cancer in men (other than skin cancer), secrete a prostate specific antigen (PSA); elevated levels of PSA in the blood suggest a possible tumor in the prostate.
Oncofetal proteins, normally found on fetal cells, may also be reexpressed by certain tumors. Elevated levels of alpha-fetoprotein and carcinoembryonic antigen in serum may indicate liver or colorectal cancer. The increasing sensitivity of such screening methods holds out the prospect that the most common forms of cancer may be detected in a “curable” stage.
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