Premium
Cancer cell‐derived IL‐1α promotes HGF secretion by stromal cells and enhances metastatic potential in pancreatic cancer cells
Author(s) -
Xu Donghui,
Matsuo Yoichi,
Ma Jiachi,
Koide Shuji,
Ochi Nobuo,
Yasuda Akira,
Funahashi Hitoshi,
Okada Yuji,
Takeyama Hiromitsu
Publication year - 2010
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21530
Subject(s) - hepatocyte growth factor , stromal cell , pancreatic cancer , paracrine signalling , angiogenesis , cancer research , medicine , autocrine signalling , cell culture , metastasis , cell growth , cancer cell , cancer , pathology , biology , receptor , genetics
Background and Objectives Interleukin (IL)‐1α 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‐1α in metastatic processes promoted by interactions between pancreatic cancer cells and stromal cells. Methods Expression of IL‐1α 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‐1α expression was closely correlated with metastatic potential, and cancer cell‐derived IL‐1α significantly promoted HGF expression by fibroblasts ( P < 0.01). HGF not only enhanced the invasiveness and proliferation of pancreatic cancer cells, but also enhanced migration 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‐1α, significantly enhanced HUVEC tube formation compared with the low liver‐metastatic cell line (Capan‐2), which does not produce IL‐1α ( P < 0.01). Conclusion Autocrine IL‐1α and paracrine HGF co‐enhance the metastatic potential of pancreatic cancer cells via both IL‐1α and HGF signaling pathways. J. Surg. Oncol. 2010;102:469–477. © 2010 Wiley‐Liss, Inc.