Cancer cell‐derived IL‐1α promotes HGF secretion by stromal cells and enhances metastatic potential in pancreatic cancer cells
- 1 April 2010
- journal article
- research article
- Published by Wiley in Journal of Surgical Oncology
- Vol. 102 (5), 469-477
- https://doi.org/10.1002/jso.21530
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. J. Surg. Oncol. 2010;102:469–477.This publication has 25 references indexed in Scilit:
- Pancreatic Cancer: A Review of the Evidence on CausationClinical Gastroenterology and Hepatology, 2008
- Cancer Statistics, 2008CA: A Cancer Journal for Clinicians, 2008
- Scatter factor expression and regulation in human glial tumorsInternational Journal of Cancer, 1996
- Emerging Multipotent Aspects of Hepatocyte Growth FactorThe Journal of Biochemistry, 1996
- Enhanced Tumorigenicity and Invasion-Metastasis by Hepatocyte Growth Factor/Scatter Factor-Met Signalling in Human Cells Concomitant with Induction of the Urokinase Proteolysis NetworkMolecular and Cellular Biology, 1996
- Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progressionBritish Journal of Cancer, 1993
- Scatter factor induces blood vessel formation in vivo.Proceedings of the National Academy of Sciences of the United States of America, 1993
- Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth.The Journal of cell biology, 1992
- Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factorCell, 1991
- Hepatocyte growth factor/hepatopoietin A stimulates the growth of rat kidney proximal tubule epithelial cells (RPTE), rat nonparenchymal liver cells, human melanoma cells, mouse keratinocytes and stimulates anchorage-independent growth of SV-40 transformed RPTEBiochemical and Biophysical Research Communications, 1991