Expression of galectin-1 in carcinoma-associated fibroblasts promotes gastric cancer cell invasion through upregulation of integrin β1

Cancer Sci. 2014 Nov;105(11):1402-10. doi: 10.1111/cas.12539. Epub 2014 Oct 23.

Abstract

Increased expression of galectin-1 (Gal-1) in carcinoma-associated fibroblasts (CAFs) has been reported to correlate with progression and prognosis in many cancers. However, rarely have reports sought to determine whether high Gal-1 expression in CAFs in gastric cancer is involved in the tumor process, and the specific mechanism by which it promotes the evolution of gastric cancer is still unknown. In this study, we cultured gastric cancer CAFs, which showed strong expression of Gal-1, and established a co-culture system of CAFs with gastric cancer cells. Specific siRNA and in vitro migration and invasion assays were used to explore the effects of the interaction between Gal-1 expression of CAFs and gastric cancer cells on cell migration and invasion. We found that the overexpression of Gal-1 in CAFs enhanced gastric cancer cell migration and invasion, and these stimulatory effects could be blocked by specific siRNA which reduced the Gal-1 expression level. A set of cancer invasion-associated genes were then chosen to identify the possible mechanism of Gal-1-induced cell invasion. Among these genes, integrin β1 expression in cancer cells was considered to be associated with Gal-1 expression. Pre-blocking of the integrin β1 expression in gastric cancer cells with siRNA could interrupt the invasion-promoting effect of CAFs with high Gal-1 expression. Furthermore, immunohistochemical assay confirmed a positive correlation between Gal-1 and integrin β1 expression. Our results showed that high expression of Gal-1 in CAFs might facilitate gastric cancer cell migration and invasion by upregulating integrin β1 expression in gastric cancer.

Keywords: Carcinoma-associated fibroblasts; Gal-1; gastric cancer; integrin β1; invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Galectin 1 / genetics*
  • Galectin 1 / metabolism
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Integrin beta1 / genetics*
  • Integrin beta1 / metabolism
  • Male
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Tumor Burden
  • Up-Regulation

Substances

  • Galectin 1
  • Integrin beta1
  • LGALS1 protein, human