Generation of a complement-derived chemotactic factor for tumor cells in experimentally induced peritoneal exudates and its effect on the local metastasis of circulating tumor cells.

摘要

A chemotactic factor for tumor cells was found in inflammatory exudate fluids induced by giving intraperitoneal injections of glycogen to Sprague-Dawley rats. The quantity of chemotactic activity and the period of time during which it could be detected correlated with the inflammatory reaction, measured by the cellular composition of the exudates and their content of protein and lysosomal enzymes. In gel filtration the chemotactic factor behaved mainly as a molecule having a molecular weight of approximately 6000 daltons. Its biologic activity was blocked by antiserums directed against C5 but not by antiserums against C3 or C4. In these two respects, the factor generated in vivo has the same properties as a previously described chemotactic factor that can be generated in vitro by proteolysis of purified C5 or C5a. Chemotactic activity was not detected in the glycogen-induced peritoneal exudates of rats depleted of serum complement by cobra venom factor. Intravenously injected Walker tumor cells arrested and formed metastases in the mesenteries of rats with peritonitis in greater numbers than in normal controls, animals depleted of complement during the experimental period, or animals given intraperitoneal injections of the vasopermeability agent, histamine. The growth of tumor cells in vitro was not promoted by peritoneal exudate fluids, nor was the number of metastases on vivo greater than in negative controls, in animals in which peritonitis was induced 24 hours after the intravenous injection of tumor cells. It is argued that chemotactic mechanisms can contribute to the formation of metastases at sites of tissue injury.