Influence of migratory blood cells on the attachment of tumor cells to vascular endothelium

Abstract

The purpose of this study was to determine whether the presence of migratory blood cells in association with tumor emboli had the capacity to alter the attachment of tumor cells to vascular endothelium. Highly metastatic RT7-4bs rat hepatocarcinoma cells were labelled with [¹²⁵]UdR before being allowed to form mixed cellular spheroids incorporating 1) resident peritoneal macrophages, 2) activated peritoneal macrophages, 3) polymorphonuclear leukocytes, 4) splenic T lymphocytes, or 5) splenic B lymphocytes derived from both normal and tumor-bearing animals. The presence of polymorphonuclear leukocytes or activated macrophages led to a considerable increase in the number of tumor cells attaching to endothelial cell monolayers in vitro. The presence of T or B lymphocytes from either normal or tumor-bearing rats was without effect on tumor attachment to endothelium. Increased tumor cell retention in the lungs was evident for mixed spheroids containing tumor cells and polymorphonuclear leukocytes compared to homotypic tumor spheroids composed of tumor cells alone. Furthermore, preinjection of polymorphonuclear leukocytes intravascularly or inoculation of tumor cells as heterotypic spheroids containing polymorphonuclear leukocytes increased lung colony formation over that obtained after inoculation of tumor cells alone. Several simple sugars were tested for their ability to block tumor cell, polymorphonuclear leukocyte or activated macrophage binding to endothelium in vitro. The results indicate that the glycosylated cell surface components mediating tumor cell attachment to endothelium are not identical with those mediating attachment of either polymorphonuclear leukocytes or activated macrophages. Medium conditioned during mixed spheroid formation was without effect on tumor cell attachment to endothelium. We conclude that the presence of some, but not all classes of leukocytes can modulate tumor cell attachment to vascular endothelium, an effect most likely mediated by a mechanism involving direct contact between the leukocytes and the endothelial cell monolayer.