Promotion of growth of tumour cells in acutely inflamed tissues.
Acute inflammatory reactions were induced in rats by the intravenous injection of cellulose sulphate (CS) or an extract of normal rat lung homogenate (LH), or by intraperitoneal injections of Compound 48/80. These treatments greatly increased survival and clonogenic growth in the lungs of rats of intravenously injected allogeneic W-256 and Y-P388 tumour cells. Increase in the dose of intravenously injected CS caused a logarithmic increase in colony forming efficiency (CFE) of tumour cells in the lungs. CFE was not stimulated by the intravenous injection of rats with pharmacological mediators of inflammation (histamine, 5-hydroxytryptamine, bradykinin and prostaglandins PGE(1) and PGF(2α)) which are released from tissues by agents which induce inflammation. Stimulation of CFE by CS occurred in adrenalectomized rats but was inhibited by treatment of rats with an anti-inflammatory steroid, dexamethasone. CFE was stimulated by CS in tumour immunized rats; the inflammatory state did not prevent the expression of immunity but "rescued" a proportion (approximately 20%) of the injected tumour cells from immunodestruction in the lungs. A higher proportion of tumours grew in the paws of rats when a small number of W-256 cells were injected interdigitally into the acute inflammatory swellings produced by the local injection of paws with LH or CS.CS is a "synthetic heparin" which causes marked prolongation of blood clotting time and also increases fibrinolytic activity of the blood. Anticoagulant treatment of rats with heparin did not affect CFE. Thus, there was no direct correlation between blood clotting time and CFE of blood borne tumour cells in the rat.The mechanisms which may be responsible for the nonspecific growth promoting effects of inflammatory reactions induced by various types of tissue injury on tumour induction and growth are discussed.
D000315:Adrenalectomy; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002279:Carcinoma 256, Walker; D002460:Cell Line; D002482:Cellulose / Q000008:administration & dosage / Q000633:toxicity; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006084:Graft Rejection; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000276:immunology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D012517:Sarcoma, Yoshida; D012701:Serotonin / Q000494:pharmacology; D014184:Transplantation, Homologous; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
D011453:Prostaglandins; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D003907:Dexamethasone; D006632:Histamine; D002482:Cellulose; D001920:Bradykinin