Cancer Cell-Derived IL-1α Promotes HGF Secretion by Stromal Cells and Enhances Metastatic Potential in Pancreatic Cancer Cells

Background and Objectives: Interleukin (IL)-1 alpha and hepatocyte growth factor (HGF) play an important role in pancreatic cancer proliferation. angiogenesis. and invasiveness The aim of this study was to investigate the cooperative role of HGF and IL-1 alpha in metastatic processes promoted by Interactions between pancreatic cancer cells and stromal cells Methods: Expression of IL-1 alpha and HGF mRNA and protein was determined by RT-PCR and ELISA The effect of HGF on metastatic potential was evaluated by proliferation, invasion, and angiogenesis assays using an in vitro system consisting of co-cultured tumor cells and stromal cells Results: IL-1 alpha expression was closely correlated with metastatic potential, and cancer cell-derived IL-1 alpha significantly promoted HGF expression by fibroblasts (P < 0 01) HGF not only enhanced the Invasiveness and proliferation of pancreatic cancer cells. but also enhanced in and proliferation of human umbilical vein endothelial cells (HUVECs) HGF significantly enhanced HUVEC tube formation (P < 0 01) Furthermore, the high liver-metastatic pancreatic cancer cell line (BxPC-3). which secretes IL-1 alpha, significantly enhanced HUVEC tube formation compared with the low liver-metastatic cell line (Capan-2). which does not produce IL-1 alpha (P < 0 01) Conclusion: Autocrine IL-1 alpha and paracrine HGF co-enhance the metastatic potential of pancreatic cancer cells via both IL-1 alpha and HGF signaling pathways J Surg Oncol 2010,102 469-477 (C) 2010 Wiley-Liss. Inc.