NATURAL HUMAN INTERFERON-ALPHA INHIBITS THE ADHESION OF A HUMAN CARCINOMA CELL-LINE TO HUMAN VASCULAR ENDOTHELIUM

The adhesion of cells to the microvascular endothelium is an essential step in the inflammatory response and metastasis, We have found that pretreatment of a human epidermoid carcinoma cell line, KB, with natur al human interferon-alpha (IFN-alpha) inhibited the binding of the mal ignant cells to human umbilical vein endothelial cells (HUVEC) in a do se- and time-dependent manner, As one of several possible mechanisms f or this inhibition, the expression of some revelant adhesion molecules on KB cell surfaces was examined after IFN-alpha treatment, Apart fro m a slight increase in the expression of integrin alpha 4 beta 1 (very late activation antigen 4, VLA-4), no changes in the expression of ot her adhesion molecules, such as sialyl Lewis X, CD44, and leukocyte fu nction-associated antigen 1 (LFA-1), which is known to be a heterodime r of CD11a and CD18, were observed after treatment with IFN-alpha. In addition, the cell viability of KB was not affected by treatment of th e cells with IFN-alpha, although the cell proliferation was markedly i nhibited, indicating that the inhibitory effect of IFN-alpha on KB cel l binding to vascular endothelium is not a result of a cytotoxic effec t of IFN-alpha. Because the metastatic process requires not only the a dhesion of tumor cells to vascular endothelium during their extravasat ion but also proliferation at distant sites, our findings from this in vitro experimental model suggest that IFN-alpha may have a potential inhibitory effect on tumor cell metastasis.