Abstract B56: Regulation of immune-related genes by integrin signaling affects the cancer cell proliferation and invasion

Abstract

Abstract Cytokines have been implicated in tumor proliferation and metastasis. Saxatillin, snake venom-derived disintegrin, is known to suppress tumor progression in vivo and in vitro but its correlation with cytokine's functions has not been known yet. We have investigated the role of immune-related genes in cancer cell proliferation and metastasis in human ovarian cancer cell (MDAH 2774). We demonstrate that saxatilin, an integrin antagonist, mitigated MDAH 2774 proliferation and invasion by reducing the level of TNF- induced matrix metalloproteinase-9 (MMP-9) and IL-8 expression in a dose-dependent manner. And Immunoblot assay of nuclear extracts of the cancer cells implicated that signal transducer and activator of transcription (STAT) is related in integrin signaling pathway. We also observed the activity of human glioma cell-invasion mediated by IL-8, as examined by a Boyden chamber assay, involved the mechanism of enhancing the actin stress fiber formation. IL-8 increased the phosphorylation of focal adhesion kinase (FAK), known to be the site of integrin clustering and nuclear translocation of STAT. We have shown here that interleukin-8 promotes the cancer proliferation and that mRNA levels of immune-related genes are regulated by disintegrin in human ovarian cancer cell line. These results demonstrate immune-related genes as a mediator of metastasis and proliferation and disintegrin would contribute in slowing of cancer development by regulating integrin signaling. (This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea Government (No.2009-0081759), KIST grant, and the Brain Korea 21 (BK21) program.) Citation Information: Cancer Prev Res 2010;3(1 Suppl):B56.