Human neutrophils facilitate tumor cell transendothelial migration

Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular en dothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) as sist the human breast tumor cell line MDA-MB-231 to cross the endothelial b arrier. We found that tumor-conditioned medium (TCM) downregulated PMN cyto cidal function, delayed PMN apoptosis, and concomitantly upregulated PMN ad hesion molecule expression. These PMN treated with TCM attached to tumor ce lls and facilitated tumor cell migration through different endothelial mono layers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan a nalysis revealed that these tumor cells expressed high levels of intercellu lar adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells signif icantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tu mor cells still possessed the ability to proliferate after PMN-assisted tra nsmigration. These results indicate that TCM-treated PMN may serve as a car rier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extrava sation.