Significance of fibrin formation and dissolution in the pathogenesis and treatment of cancer.
Despite increased concentration of plasminogen activators in malignant tumors, fibrinolytic potential in blood of cancer patients and tumor tissue is low. At the same time histochemical and microscopic examination revealed the presence of fibrin-like material coating tumor cells. It is postulated in the present paper that the increased concentrations of -SH groups and arginine-rich peptides, and the activation of tissue transglutaminases in the tumor tissue are responsible for the resistance of the fibrin coat to enzymatic degradation. The fibrin coat, in turn, causes neoplastic cells not to be recognized by the immunological system and thus makes them immune to the attack by the natural killer cells. Administration of naturally occurring, but diminished in cancer, derivatives of alpha ketoaldehydes resistant to glyoxalases, reverses the effect of -SH and arginine-rich peptides, and reactivates fibrinolysis. Consequently, removal of the fibrin coat from tumor cells makes them vulnerable to the attack of killer cells and their subsequent elimination.
Egyud
L G
LG
Cell Research Corporation, Newton, MA 02159.
Lipinski
B
B
D001120:Arginine / Q000378:metabolism; D005337:Fibrin / Q000096:biosynthesis* / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D011765:Pyruvaldehyde / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism
D013438:Sulfhydryl Compounds; D011765:Pyruvaldehyde; D005337:Fibrin; D001120:Arginine; D011503:Transglutaminases