Analysis of aprotinin-induced enhancement of metastasis of Lewis lung tumors in mice.
The antiproteinase, aprotinin, has been reported by some workers to inhibit the growth and development of a number of different types of primary cancers in animals; however, its effects on metastasis particularly need clarification. As proteolytic enzymes are thought to be involved in some steps of metastasis, we have investigated the effects of aprotinin on the spontaneous metastasis of Lewis lung (LL) tumors in mice together with its effects on the detachment of cells from primary LL cancers, the development of lung tumors from i.v. injections of LL cells, LL cell adhesion in vitro, and LL cell retention in the lungs. The results suggest that the metastasis-enhancing effect of aprotinin is due partly to promotion of the retention of circulating cancer cells at the vascular endothelium. As these effects could well occur with cancers in general, we conclude that antiproteinases may do more harm than good if used in cancer therapy.
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D007611:Aprotinin / Q000009:adverse effects / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology; D009360:Neoplastic Cells, Circulating
D000970:Antineoplastic Agents; D007611:Aprotinin