Resistance to IL-1 anti-proliferative effect, accompanied by characteristics of advanced melanoma, permits invasion of human melanoma cellsin vitro, but not metastasis in the nude mouse

Open Access
Publisher Website
Google Scholar
Abstract
We reported earlier that IL‐1 inhibits the growth of human melanoma cells (A375‐6), and that these cells become resistant to IL‐1 after prolonged periods of culture. The resistant cells constitutively produce IL‐α and IL‐6 with IL‐6 production was induced by endogenous IL‐1 in an autocrine manner. The cells are also resistant to IL‐6 anti‐proliferative effects. In the present study, we show that the resistant clones exhibited up‐regulated expression of intercellular‐adhesion molecule 1 (ICAM‐1) and vitronectin receptor (integrin αvβ3) when compared with the IL‐1‐sensitive clone, A375‐6. Moreover, these IL‐1‐resistant clones exhibited many other metastatic characteristics, such as expression of IL‐8 mRNA, production of matrix metalloproteinases (MMP‐2 and MMP‐9), and augmented invasion activity. However, contrary to our expectations, the IL‐1‐resistant cells did not exhibit experimental metastasis in a nude‐mouse model, similarly to the IL‐1‐sensitive parental A375‐6 cell line. In contrast, the highly metastatic clone A375‐SM exhibited αvβ3 expression at a level comparable to that of the IL‐1‐resistant cells, but expressed low or no ICAM‐1, metalloproteinase and displayed little in vitro invasion activity. These results show that the metastatic characteristics of IL‐1‐resistant cells are not sufficient to produce metastasis in vivo and suggest that these resistant clones may provide a good model system for characterizing the molecular mechanisms of metastasis. Int. J. Cancer 71:416‐421, 1997. © 1997 Wiley‐Liss Inc.