Cancer cell-derived IL-1α promotes HGF secretion by stromal cells and enhances metastatic potential in pancreatic cancer cells

Donghui Xu, Yoichi Matsuo, Jiachi Ma, Shuji Koide, Nobuo Ochi, Akira Yasuda, Hitoshi Funahashi, Yuji Okada, Hiromitsu Takeyama

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)469-477
Number of pages9
JournalJournal of Surgical Oncology
Volume102
Issue number5
DOIs
Publication statusPublished - 01-10-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Fingerprint Dive into the research topics of 'Cancer cell-derived IL-1α promotes HGF secretion by stromal cells and enhances metastatic potential in pancreatic cancer cells'. Together they form a unique fingerprint.

  • Cite this