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BIOLOGY OF CANCER – Academic Script Course Name: Zoology First Year B.Sc. Paper No. & Title: Z 102 B Cell Biology Topic No. & Title: Topic No : 19 Biology Of Cancer Unit : 1 1 Academic Script: 1. What is Cancer? Cancer is defined as a disease that is caused by changes in a cell that leads to the loss of basic cell control and function. When a cell turns Cancerous it loses its regulation over biochemical, metabolic and cell division processes that leads to the loss of cell structure and function. The cell loses its normal properties. This is termed as Cell Transformation. 2. Common terms/types: The cell transformation that was discussed is also called as Neoplasia. Neoplasia means “New Growth” Cancers are named according to the cell/organ of origin: e.g. : Cancer of the colon : colon cancer Basal Cell :basal cell carcinoma CARCINOMA: Cancer originating in skin/epithelial tissues SARCOMA: Cancer in bone, cartilage, adipose tissues, blood vessels (Connective tissue) LEUKAEMIAS are Cancers originating in blood forming tissues, bone marrow. LYMPHOMA is a type of cancer with its origin in the Immune system BENIGN TUMORS are non-cancerous. 2 The cells are altered but they do not spread or tissues, the tumor on the left is Benign. invade other MALIGNANT TUMORS are cancerous tumors where the cells are altered and they also invade and spread and cause tumors to other organs. The tumor on the right is malignant. 3.CHARACTERISTICS OF A CANCER CELL: Uncontrolled cell division CANCER CELLS HAVE THE PROPERTY OF IMMORTALITY OR INDEFINITE CELL LIFE WHERE THEY CONTINUE TO GROW AND DIVIDE WITHOUT DYING Normal cells show finite growth, controlled cell division, limited survival in culture o On the other hand transformed cells are immortal and can divide and grow indefinitely. This is because cancer cells lose control over cell division. 4.Loss of cell-cell contact inhibition: Normal cells in a culture will stop growing when the plasma membranes come in contact with each another When two normal cells come into contact, one or both will stop moving and then begin to move in another direction. This inhibition of cell division and growth after contact is termed contact inhibition. Cancer cell lose this property and grow and divide indefinitely. 5.Loss of cell adhesion: Then the rate of division slows down. Contact of the plasma membranes of the cells inhibits growth and division. Transformed/ cancer cells on the other hand usually do not stop dividing after forming a monolayer. Division continues until several layers of cells are formed. 3 If cells are growing in a culture, the cells plasma membrane will adhere to the support. They will continue to grow and divide at a regular interval of 24 hours, until they form a single monolayer. Thus transformed cells grow and divide continuously until they pile up to form a TUMOR. Cancer cells also have the property of Angiogenesis, to increase their own blood supply. 6.Cancer Cells have a loss of anchorage dependence: Cancer cells do not require a rigid substratum for anchorage, to grow whereas normal cells do. Transformed cells grow even when they are not attached to the substratum. This loss of anchorage is a characteristic of transformed cells, which form malignant tumors. 7. Cancer cells lack cell-cell communication: Cancer cells apparently lack proper recognition and communication with adjacent cells. Even electrical communication between cells is reduced. 8. Changes in nucleus of cancer cells: Nucleus enlarged, irregular- with blebs and infoldings in the nuclear membrane, causing fragmentation in nucleus. As seen in the figure, nucleoli are many and irregular and the chromatin appears clumped with proteins. Chromosomal morphology altered with increased chromosomal aberration. 9.Molecular changes in cell membranes: Cancerous cells do not differ from normal cells in their relative amounts of membrane phospholipids. 4 Some lipids eg. Gangliosides become reduced when a cell turns cancerous. Enzymes that are responsible for their biosynthesis are also reduced. Tumors have simple and fewer lipids. Some membrane glycoprotein and proteins are reduced ,they start disappearing when they are transformed to a cancerous one. The mobility of the surface proteins increases in transformed cells, thus permitting easier agglutination of tumor cells. The membrane forms blebbs. 10.Changes in cell surface antigens: Cancer cells develop new cell surface antigens. Plasma membranes of transformed cells contain antigens not present in normal cells. Thus in cells transformed by adenoviruses a new antigen: T antigen appears. Cells transformed by the Epstein-Barr virus contain a new antigen - EB nuclear antigen (EBNA). 11. Cytoskeletal Disorganisation is seen in a Cancer Cell In a cell a cytoskeleton comprises of microtubules and microfilaments, which control the cell movement, shape and structure. In transformed cancer cells such elements are fewer in number and thinner. Cytoskeleton undergoes depolymerization, the microtubules disaggregate and microfilaments (actin, myosin) disappear or diffuse. Cytoskeletal proteins become less organized but the fluidity of lipids remains, with increased mobility of cell membrane proteins. Cytoskeleton disorganization causes a constant and uncoordinated throwing out and retraction of blebs, microvilli and processes from the cell surfaces. 5 12.Cancer cells have the property of De-differentiation: Cancer cells were once fully differentiated cells but on cell transformation they start losing their specialized properties. In most mammalian tissues the enzyme aldolase A, B and C. Isozymes A and C - in embryonic tissues, differentiated tissues. has isozymes Isozyme B - in adult In some tumours, especially in poorly differentiated and fast dividing cancers like hepatomas, isozyme B is replaced by isozyme A, the embryonic form. 13. Cancer cells require less oxygen and nutrients: When cancer cells are cultured they grow rapidly and show lower serum requirements. Transformed cells can grow in a culture medium containing much less serum than required by normal cells. This is because of their less need for factors to lower their intracellular cAMP (cyclic- AMP) level to trigger mitosis 14. Cancer cells show unique properties such as invasiveness: Transformed cells have ability to invade other tissues. This invasiveness may be due to changes in the plasma membrane or proteases released by the cells. Cancer cell secrete protease enzymes like collagenase which digest the proteins of the basement membrane on which they rest. This creates a gap in the basement membrane through which the cancer cell moves and enters the neighbouring tissue, blood stream or lymph. 15. Metastasis: 6 Cancer cells lose their normal tissue integrity property and thus can leave their neighbouring cells and move away from the tissue. Metastasis is the process in which neoplastic/cancer cells dislodge from their tissue of origin, enter the blood stream or lymph and spread to other tissues, where they lodge and form a new tumor. They cause the cells at the new site to be altered. Thus Cancer spreads to other organs of the body. 16. Cancer cells also show Altered metabolism: In a cancerous cell there is an increased rate of glycolysis whereas Oxidative (aerobic) respiration decreases. Glycolysis (anaerobic respiration) increases. Lactic acid production increases in cells of solid tumours, with increase in uptake of glucose. Increase in glycolysis is due to lower normal oxidation. ATP synthesis and tumour mitochondrial activity increases. This high energy requirement of actively dividing cancer cells causes an adaptive response. 17. Cancer cells have Uncontrolled biosynthesis: Cancer cells cannot respond to signals that control their metabolic and biosynthetic activities. Hence large amounts of proteolytic enzymes are secreted by most cancer cells, which have adverse effects on the cell. A cancer cell secretes a protease, the cell factor to form a plasmin, a proteolytic enzyme which removes many proteins projecting from the cell surface. This signals the cell into division. 18. The cell cycle is altered in cancer cells: 7 In its cell cycle, Cancer cells do not follow the same control mechanisms as a normal cell. The checkpoints control the division rate of normal cells but such mechanisms are not found in a cancer cell. 19. Conclusion: Hence, we know that Cancer is a dreaded decease, which results from uncontrolled, Morphological, biochemical and functional changes in a cell, which then spreads to Invade other tissues. 8