In vitro analysis of the melanoma endothelium interaction increasing the release of soluble intercellular adhesion molecule 1 by endothelial cells

Melanoma cells constitutively release intercellular adhesion molecule 1 (IC AM-1) as soluble ICAM-1 (sICAM-1), and its levels are elevated in melanoma patients and correlate with disease progression. However, this correlation is not absolute, suggesting that specific characteristics of neoplastic cel ls and/or ICAM-1-positive non-neoplastic cells may influence the amounts of circulating sTCAM-1. In this Study,we found a weak correlation (r = 0.55; r(2) = 0.3) between sICAM-1 release by 40 metastatic melanomas (36 primary cultures and 4 cell lines), and ICAM-1 expression on neoplastic cells. In a ddition, melanoma-secreted interleukin-1 alpha (IL-1 alpha) (1/40) but not vascular endothelial growth factor (VEGF) (29/40), significantly (P < 0.05) up-regulated the shedding of sICAM-1 by human umbilical vein endothelial c ells (HUVEC). This was completely abolished by IL-1 alpha/beta neutralizing antibodies both at the protein and mRNA level. Altogether, our results sug gest that (i) the extent of sICAM-1 release is distinctive for individual m elanomas and can be independent of ICAM-1 expression; (ii) tumor endothelia may sustain levels of sICAM-1 in selected melanomas; (iii) melanoma;releas ed VEGF does not affect ICAM-1 expression and sICAM-1 release by HUVEC. Mel anoma-derived sICAM-1 inhibits cell-mediated cytotoxicity of melanoma cells ; therefore, constitutive levels of sI-CAM-1 release and IL-lc( secretion b y individual melanomas can differentially influence tumor progression and t he clinical effectiveness of cytotoxic-cell-based vaccines.