Effect of interleukin-8 on production of tumor-associated substances and autocrine growth of human liver and pancreatic cancer cells

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• 作者：Megumi Miyamoto ; Yukihiro Shimizu ; Kazuhiko Okada ; Yoshiro Kashii ; Kiyohiro Higuchi and Akiharu Watanabe
• 关键词：Key words Liver cancer ; Pancreatic cancer ; Autocrine growth factors ; Sialyl ; Lewisa ; Tumor metastasis
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：1998
• 出版时间：September 1998
• 年：1998
• 卷：47
• 期：1
• 页码：47-57
• 全文大小：597 KB

文摘

We have previously reported that human liver cancer cell lines produce interleukin-8 (IL-8) at high levels. Those tumor cells appeared to express 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 cells, 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 antisense oligonucleotides. Suppression of IL-8 production resulted not only in inhibition of cell growth, but also in an increase in the concentrations of some tumor-associated substances such as carbohydrate antigen 19-9 (CA19-9) in the medium. These data indicate that IL-8 produced by human liver and pancreatic tumors may act as an autocrine growth factor and may control the production of some tumor-associated substances. Furthermore, surface expression of sialyl-Lewisa, which is a ligand for ELAM-1 on human umbilical vein endothelial cells (HUVEC), HuCC-T1 and HuP-T4 cells was decreased and the attachment of these tumor cells to HUVEC was inhibited by treatment with IL-8 antisense oligonucleotide. Since the soluble form of CA19-9 (sialyl-Lewisa) was shown to inhibit the tumor cell binding to HUVEC, the decrease in release of CA19-9 into the medium and increase in the expression of sialyl-Lewisa 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 produced by tumor cells may function as an autocrine growth factor and affect tumor cell dissemination.