Cross-talk between human monocytes and cancer cells during reactive oxygenintermediates generation: The essential role of hyaluronan

Human monocytes exhibit considerable cytocidal activity against tumor (but not normal cells) associated, at least partly, with the generation of react ive oxygen intermediates (ROIs). The present study examined the role of sur face determinants and hyaluronan (HA) in the induction of ROI production by human monocytes stimulated with cancer cells, as measured by luminol-enhan ced chemiluminescence (CL). The inhibitory effect of monoclonal antibodies (MAbs) indicated the engagement of CD18, CD29 and CD44 adhesion molecules. Preincubation of monocytes and tumor cells, expressing CD44 determinants, w ith either anti-CD44 MAb or HA inhibited CL generation. Addition of HA to m onocytes decreased the expression of CD44 and induced CL response. Supernat ants from the cultures of tumor cells stimulated CL response of monocytes, an effect that was abolished by treatment of the supernatants with hyaluron idase (HAase) or by preincubation of monocytes with an anti-CD44 MAb. These results indicate that several surface molecules of monocytes, including CD 44, are required to trigger the generation of ROI after their contact with tumor cells, whereas HA overexpressed on some cancer cells may allow monocy tes (via CD44) to distinguish between transformed and normal cells. However , blocking of CD44 on monocytes by free HA dampens their response to tumor cells. Taken together, these observations suggest that the presence of HA i n the tumor stroma may modulate effector functions of infiltrating macropha ges and their interactions with cancer cells in situ. (C) 2001 Wiley-Liss, Inc.