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Effect of interleukin-8 on production of tumor-associated substances and autocrine growth of human liver and pancreatic cancer cells
Authors:Megumi Miyamoto  Yukihiro Shimizu  Kazuhiko Okada  Yoshiro Kashii  Kiyohiro Higuchi  Akiharu Watanabe
Institution:(1) The Third Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama City, Toyama, 930-0152, Japan e-mail: yukihirotym@cc.umin.u-tokyo.ac.jp Tel.: +81-764-34-2281; Fax: +81-764-34-5027, JP
Abstract: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. Received: 4 February 1998 / Accepted: 6 May 1998
Keywords:Liver cancer  Pancreatic cancer  Autocrine growth factors  Sialyl-Lewisa  Tumor metastasis
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