DIFFERENTIAL-EFFECTS OF INTERLEUKIN-1-ALPHA (IL-1-ALPHA) OR TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) ON MOTILITY OF HUMAN-MELANOMA CELL-LINES ON FIBRONECTIN

Interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF- alpha) induce a motogenic response in a number of benign and malignant cells. We examined the chemokinetic effects of these cytokines on the cell migration of four melanoma cell lines on fibronectin using modif ied Boyden chambers and video-time lapse analysis. Flow cytometry anal ysis of IL-1 receptors, TNF receptors, and shifts in beta(1) integrin expression were correlated with the effects of these cytokines on cell migration on fibronectin. The four melanoma cell lines exhibited hete rogeneous expression of types I and II IL-1 receptors as well as p60 T NF receptors. Scant p80 TNF receptor expression was detected on only o ne cell line. Three of four melanoma cell lines demonstrated type I IL -1 receptors by Western blotting. IL-1 alpha and TNF-alpha induced het erogeneous modulation of beta(1) integrin expression in the four melan oma cell lines tested; downward shift of the alpha(2), alpha(3), alpha (4), and beta(1) integrin subunits was detected among three of the mel anoma cell lines as were upward shifts of the alpha(4), alpha(5), and alpha(6) integrin subunits among three of the melanoma cell lines. IL- 1 alpha and TNF-alpha induced enhanced migration of fibronectin in one of the melanoma cell lines and were related to an upward shift in the alpha(4) and alpha(5) integrin subunit expression. Taken together, th e findings indicate that expression of a particular receptor for IL-1 or TNF does not necessarily signal a motogenic response in melanoma ce lls, but induces heterogeneous shifts in beta(1) integrin expression. However, up-regulation in alpha(4) and alpha(5) integrin subunits appe ars to relate to enhanced migration on fibronectin.,