Notes from Principles of Cancer Biology Chapter 2 Read before lecture 5 The distinctive feature of tumor growth is not the speed of cell division but it s uncontrolled nature Contact inhibition to refer to the decrease in cell motility that occurs when cells make contact with one another in culture Density dependent inhibition of growth routinely used when referring to the inhibition of cell division that occurs in crowded cultures Cancer cells are less susceptible to density dependent inhibition of growth than are their normal counterparts When they are provided with an appropriate solid surface spread out and begin to proliferate They are anchorage dependent In contrast most cancer cells grow well not just when they are anchored to a solid surface but also when they are suspended in a liquid or semisolid medium So they are anchorage independent Extracellular matrix An insoluble meshwork of proteins and polysaccharide fibers that fills the spaces between neighboring cells Cells attach themselves to the extracellular matrix through cell surface proteins called integrins which bind to molecular present in the matrix Apoptosis is an important safeguard for maintaining tissue integrity because it prevents normal cells from floating away and setting up shop in another tissue Cancer cells are anchorage independent so they do not need this A very large difference between cancer and normal cells in their lifespan Normal cells will usually divide only a limited number of times before they die Cancer cells have no such limit and behave as if they were immortal The answer lies in the mechanism used to replicate DNA Placing such noncoding telomere DNA at the ends of each chromosome ensures that a cell will not lose any important information when DNA molecules are shortened slightly during replication since telomeres get shorter with each cell division they provide a counting device for tracking how many times the telomeres became extremely short and are in danger of disappearing entirely When this happens the telomeric DNA becomes too short to bind telomeric capping proteins or generate a loop exposing a bare end of double stranded DNA In normal cells such a hazardous outcome is prevented by a mechanism in which the unprotected DNA at the end of a chromosome triggers a pathway that halts cell division or triggers cell death Germ bone marrow cells prevent excessive telomere shortening by producing an enzyme called telomerase which adds new copies of the telomeric repeat sequence to the ends of existing DNA molecules The presence of telomerase therefore allows cells to divide indefinitely without shortening Most cancer cells circumvent this problem by activating the gene that produces telomerase thereby causing new copies of the telomeric repeat sequence to be continually added to the ends of their DNA molecules The cells of multicellular animals do not normally divide unless they are stimulated to do so by appropriate signaling protein known as a growth factor Growth factors exert their effects by binding to receptor proteins located in the plasma membrane that forms the outer boundary of all cells Some cancer cells achieve this autonomy by producing their own growth factors thereby causing cell proliferation to be stimulated without the need for growth factors produced by other cells Similarly other cancer cells possess abnormal receptors that are permanently activated causing cell division to occur whether growth factors are present or not For division cells pass through a series of discrete stages called G1 S G2 and M phase Called the cell cycle Taken together the G1 S and G2 phases are collectively referred to as interphase In such cases the cell cycle is halted in late G1 at a point referred to as the restriction point Other key points in the cell cycle is controlled by proteins known as cyclin dependent kinases CDK is a protein kinase A term referring to a class of enzymes that regulate the activity of targeted protein molecule by catalyzing their phosphorylation The ability of growth factors to promote passage through the restriction point by stimulating the production of CDK cyclins that phosphorylate Rb is just one example of how the cell cycle is controlled by external and internal factors that determine whether or not a cell should divide Such alterations cause an excessive production of the CDK Cyclins that phosphorylate the Rb protein thereby providing an ongoing stimulus for cells to pass through the restrictions point and pass In addition to the loss of restriction point control cancer cells frequently exhibit defects n the checkpoint pathways Cells infected with viruses often envoke apoptosis to trigger their own destruction thereby limiting reproduction and spread of the virus P53 protein is heavily involved in apoptosis P53 coding gene is defective in cancer cells Molecules capable of provoking an immune response are referred to as antigens To trigger an efficient immune response an antigen must be degraded and processed by specialized antigen presenting cells
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