The effect of interleukin-1 receptor antagonist on metastasis through inhibiting HGF secretion in human colon cancer cell lines / 中华普通外科杂志

ABSTRACT

Objective The aim of this study was to investigate the co-operative role of HGF and IL-1ra in metastatic processes by interactions between colon cancer cells and stromal cells in their microenvironment.Methods Expression of IL-1α,HGF and c-Met mRNA and proteins were determined by RT-PCR and Western blot.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 enhanced the migration and proliferation of human umbilical vein endothelial cells (HUVECs),and angiogenesis (P ＜ 0.01).The high liver-metastatic colon cancer cell line (HT-29),which secretes IL-1 α,significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2),which does not produce IL-1 α (P ＜ 0.01).IL-1 ra significantly inhibit migration,proliferation and angiogenesis (P ＜ 0.01).Conclusions Autocrine IL-1α and paracrine HGF enhance the metastatic potential of colon cancer cells;IL-1ra inhibit the metastatic potential of colon cancer cells by blocking IL-1α and HGF signaling pathways.