EFFECT OF INTERLEUKIN-8 ON PRODUCTION OF TUMOR-ASSOCIATED SUBSTANCES AND AUTOCRINE GROWTH OF HUMAN LIVER AND PANCREATIC-CANCER CELLS

We have previously reported that human liver cancer cell lines produce interleukin-8 (IL-8) at high levels. Those tumor cells appeared to ex press two kinds of IL-8 receptor on their surface. In order to analyze the role of IL-8 on the biological characteristics of those tumor cel ls, we suppressed IL-8 production from human liver (HuH-7 and HuCC-T1) and pancreatic cancer cell lines (HuP-T4) by treatment with IL-8 anti sense oligonucleotides. Suppression of IL-8 production resulted not on ly in inhibition of cell growth, but also in an increase in the concen trations of some tumor-associated substances such as carbohydrate anti gen 19-9 (CA19-9) in the medium. These data indicate that IL-8 produce d by human liver and pancreatic tumors may act as an autocrine growth factor and may control the production of some tumor-associated substan ces. Furthermore, surface expression of sialyl-Lewis(a), which is a li gand for ELAM-1 on human umbilical vein endothelial cells (HUVEC), HuC C-T1 and HuP-T4 cells was decreased and the attachment of these tumor cells to HUVEC was inhibited by treatment with IL-8 antisense oligonuc leotide. Since the soluble form of CA19-9 (sialyl-Lewisa) was shown to inhibit the tumor cell binding to HUVEC, the decrease in release of C A19-9 into the medium and increase in the expression of sialyl-Lewis(a ) on the cell surface may suggest that IL-8 production from the tumor cells enhances metastatic potential by augmenting the binding activity of the tumor cells to HUVEC. These data demonstrate that a cytokine p roduced by tumor cells may function as an autocrine growth factor and affect tumor cell dissemination.