Enhancement of integrins by interleukin-1alpha,and their relationship with metastatic and invasive behavior of human pancreatic ductal adenocarcinoma cells

BACKGROUND AND OBJECTIVES: Adhesion and invasion of tumor cells to extracellular matrix (ECM) proteins play an important role in tumor metastasis formation. We investigated the enhancement of adhesive and invasive behavior to ECM proteins of human pancreatic cancer cells by interleukin-1alpha (IL-1alpha) to examine the mechanism of adhesion and invasion of metastatic human pancreatic cancer cells to ECM proteins. METHODS: The enhancement of integrin subunits by IL-1alpha was examined by cellular enzyme-linked immunosorbent assay (CELISA) in two metastatic human pancreatic cancer cell lines (BxPC-3 and SW1990) and two nonmetastatic pancreatic cancer cell lines (PaCa-2 and PANC-1). In addition, assays of cancer cell adhesion and invasion to ECM proteins were performed to investigate whether increased integrin expression affected the invasive interaction between cancer cells and the putative integrin ECM ligands. RESULTS: Expression of the alpha6 subunit by metastatic cancer cells was enhanced by IL-1alpha. Metastatic cancer cells also exhibited preferential adherence and invasion to laminin compared with nonmetastatic cancer cells, and this was enhanced by IL-1alpha. CONCLUSIONS: The enhancement of alpha6beta1-integrin by Il-1alpha acting through IL-1RI, as well as the expression of alpha6beta1-integrin, plays an important role in metastasis formation in pancreatic cancer