Alteration of Integrin Expression by Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Human Pancreatic Cancer Cells


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Abstract

IntroductionPancreatic cancer cells express a number of functionally active integrins that are related to their adhesive and invasive abilities.AimsTo determine whether glial cell line-derived neurotrophic factor (GDNF) influences the expression of integrins in pancreatic cancer cell lines and to elucidate the mechanisms of adhesion and invasion to extracellular matrix (ECM) proteins.MethodologyThe expression of integrin subunits and the alteration of their expression by GDNF were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in pancreatic cancer cell lines (MIA PaCa-2 and BxPC-3). Assays of adhesion and invasion of cancer cells to ECM proteins were conducted to investigate whether increased integrin expression affects the interaction between cancer cells and putative integrin ECM ligands.ResultsExpression of some of the integrin subunits in pancreatic cancer cells was enhanced by GDNF. The enhancement and associated increase in adhesive and invasive ability by GDNF were inhibited by blocking the GDNF receptor or the integrin β1 subunit.ConclusionsIn pancreatic cancer, the enhancement of integrin expression by GDNF signaling through the GDNF receptor strongly influences adhesion and invasion to ECM proteins.

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