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CANCER VS NORMAL CELLS
Cancer cells do not grow or divide faster than normal cells, although many people believe that, and most forms of chemotherapy were designed on the assumption that they grow faster. Actually, what makes cells cancerous is the lack of control of cell growth, so that they keep on growing without limit, even if slowly. On the other hand, some kinds of cancer cells do grow quite rapidly, even if not faster than certain normal cell types, such as those in the bone marrow that constantly replace blood cells, and those in the intestinal lining and skin (including hair follicles) that constantly renew those structures. In one form of lymphoma, the abnormality has nothing to do with growth or division at all, but instead is a lack of apoptosis (programmed cell death), so that the cells accumulate without limit. Benign versus malignant: When the growth of cells is uncontrolled, but the cells do not migrate or otherwise spread abnormally, and so remain together in a mass, they are said to be benign. Despite the usual connotations of the word benign, a benign tumor is not good for you - and can even be fatal if located in certain places like the brain, where it cannot be removed and where its growth alone can fatally damage indispensable tissues. When cells not only lack growth control but also move without control, in the sense of penetrating other tissues and otherwise spreading through the body, then they are said to be malignant. Lymphomas and leukemias inherently spread in this way, but vary widely in the degree to which they colonize bone marrow, lymph nodes etc.
Uncontrolled cell growth: --> benign tumor Cancer cells would not be malignant unless their locomotion were also out of control, not just their growth. The phenomena of contact inhibition (of cell locomotion) and contact paralysis (of cell surface movements) are believed to be reflections of the mechanism by which the motility of normal cells is controlled, with this control mechanism being part of what is defective about malignant cells. The evidence for this latter conclusion was that several kinds of cancerous cells were shown to be less susceptible to contact inhibition than equivalent normal cells: they overlapped more, they continued forward spreading and ruffling along parts of their margins that had come in contact with other cells, and so on. Such behavior is also seen in normal macrophages and polymorphonuclear leucocytes, which makes sense because it is part of the normal differentiated phenotype of those cell types to penetrate invasively through tissues. On the other hand, some cell lines that are malignant in vivo seem not to lack either contact inhibition or contact paralysis in culture. Furthermore, it has been argued that contact inhibition depends too much on the nature of the culture substratum, glass or plastic, to be directly relevant to what goes on inside the body. In my opinion, the real obstacle has been the lack of certainty about what actually gets inhibited, at a mechanistic or molecular level, when ruffling is paralysed by contact and a cell stops, turns, or reverses direction, apparently as a result of its "propulsive motor" having been locally inhibited. As was discussed earlier in this course, the evidence now points to actin assembly, and/or the coupling of newly assembled actin to transmembrane "tine proteins" or protein complexes, along the advancing cell margin. The point is that if the "ruffling" that is being paralyzed corresponds to actin assembly, etc., this would imply that contact paralysis amounts to an inhibition of actin assembly near cell-cell adhesions; conversely, failure of this paralysis in malignant cells would imply that part of the invasiveness of cancer cells may result from an increased ability to continue actin assembly near contacted cell margins. This subject obviously deserves more research.
Behavioral and structural abnormalities of cancer cells in tissue culture:
*Redistribution of cytoplasmic actin from stress fibers to lamellipodia. *Increased numbers of areas of marginal ruffling. *Lack anchorage dependence (i.e. can grow and synthesize DNA, even without a solid substratum). *Decreased adhesiveness, largely because of reduced fibronectin (the cell-collagen linking protein). *Weakened cellular contractility and traction. *Ability to spread on less adhesive substrata (presumably because of weakened contractility). *Abnormally anaerobic metabolism; secretion of much lactic acid (even with of plenty of oxygen). *Continue to grow at serum concentrations much lower than required by normal cells. *Immortal in tissue culture; can grow indefinitely in culture without undergoing senescence. * ...and many other differences
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