What Abnormality of cancer cells makes them invasive

What Abnormality of cancer cells makes them invasive - What...

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
What Abnormality of cancer cells makes them invasive? It's not that normal body cells can't crawl, because almost every differentiated cell type will crawl if put in tissue culture, on glass or plastic (or a fibrin clot, or a collagen gel). So the real question is: what allows cancer cells to move without whatever normal control mechanisms keep cells in place, once embryonic development is complete? It's not even known how much "to-and-fro" locomotion continues among body cells throughout life. The following abnormalities have been proposed as explanations for the abnormal invasiveness of cancer cells: a) Secretion of proteolytic enzymes by the cancer cells. b) Secretion of enzymes that activate pro-enzymes that are already present in tissues (that digest fibrin). c) Abnormally reduced amounts of adhesion molecules. * Specifically, the protein " fibronectin " is reduced in amount in many cancer cells. Originally it was named Large Extracellular Transformation Sensitive Protein L.E.T.S. (it was separately discovered as "cold insoluble globulin" and as "spreading factor" Adding higher concentrations of fibronectin to cancer cells can make them look more normal. Fibronectin binds to integrin in the plasma membrane, and to fibrin and collagen. Note: Several researchers found that if you dissociate and randomly mix cancer cells and their closest normal equivalents, then they consistently sort out, with the cancer cells in the exterior position. My continued interest in Steinberg's theory, and all that, is largely due to this fact. (although I have not done research on sorting by cancer cells) If you culture non-cancerous cells on less adhesive solid substrata, like untreated polystyrene, then their shapes become similar to the shapes than cancer cells have on adhesive substrata, like glass. d) Weakened force of traction. You have seen the video of phorbol ester tumor promoter causing a very dramatic reduction of wrinkling of rubber substrata. Treatment of certain cancerous cells with dibutyryl cyclic AMP causes certain cancerous cells to increase the force of their traction, and to develop more acto- myosin stress fibers (Sort of the reverse of the tumor promoter effect, but slower and using different cells). I wonder if the vimentin "knock out" mouse cells, used by those researchers in Germany, would be any more invasive than equivalent cells in normal mice. Either a negative or a positive result would be interesting. I regret that those authors did not pick up on those parts of our research that found a correlation between weakened traction and increased invasiveness. I hope they will also "challenge" this "dogma". e) Disorganized acto-myosin stress fibers. Not only can this difference simply be observed by fluorescent staining, but much research has been done using mutant forms of small GTPase oncogene proteins rho , rac and cdc-42 ). These have similar amino acid sequences and folding structures to the ras gene, which about the most deadly of all oncogenes. ("R.HO." originally stood for "Ras Homology").
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 11/05/2011 for the course BIOL 446 taught by Professor Staff during the Fall '10 term at UNC.

Page1 / 5

What Abnormality of cancer cells makes them invasive - What...

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online