The biological significance of the almost constant presence of macrophages in the tumoral microenvironment is an issue debated by several authors. The major difficulty in understanding the role played by tumor-associated macrophages (TAMs) in
tumor progression is due to the contrasting effects of TAMs found in different studies. In addition, there is a limited information on which of the many biological activities expressed by TAMs are critical in inducing stimulatory or inhibitory effect on
tumor growth. The aim of our study was: (a) to explore to what extent cyclo-oxygenase-2 (COX-2) in TAMs associated with human
melanoma is expressed at different stages of
tumor progression; and (b) to explore whether COX-2 expression in TAMs is stimulated by
melanoma cells. In order to answer this question, we determined COX-2 positive TAMs associated with cutaneous
melanocytic nevi, in situ, invasive and metastatic
melanoma. In addition, we investigated whether COX-2 is expressed in peritoneal thioglycollate-elicited macrophages after co-cultivation with murine
B16 melanoma cells. We found that COX-2-positive TAMs, as revealed by immunohistochemical analysis, were rare in common
nevi and "
dysplastic nevi", but present in a high percentage in in situ and thin
melanoma. COX-2-positive TAMs were also found in more advanced
tumors and metastatic
melanoma, although at a significantly lower percentage in these latter. The in vitro protocol revealed that COX-2 was expressed in peritoneal macrophages upon contact with B16 murine
melanoma cells, but not with normal murine fibroblasts. On the whole, the results of in vivo and in vitro studies suggest that COX-2 expressed in TAMs appears to act as an effective
biomarker of
melanoma progression, and
melanoma cells themselves might stimulate COX-2 in macrophages.