The effect of interleukin-1 receptor antagonist on metastasis through inhibiting HGF secretion in human colon cancer cell lines
10.3760/cma.j.issn.1007-631X.2015.06.014
- VernacularTitle:白细胞介素1受体拮抗因子通过抑制肝细胞生长因子的分泌影响结肠癌的新生血管形成
- Author:
Jiachi MA
;
Quan CHEN
;
Weipeng ZHAN
;
Yiping LI
;
Yuanhui GU
;
Meiling LIU
- Publication Type:Journal Article
- Keywords:
Colonic neoplasms;
Interleukin-1 receptor antagonist protein;
Neovascularization,pathologic;
Hepatocyte growth factor
- From:
Chinese Journal of General Surgery
2015;30(6):471-475
- CountryChina
- Language:Chinese
-
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.
