Galectin-1 accumulation in the ovary carcinoma peritumoral stroma is induced by ovary carcinoma cells and affects both cancer cell proliferation and adhesion to laminin-1 and fibronectin

Lab Invest. 2003 Mar;83(3):377-86. doi: 10.1097/01.lab.0000059949.01480.40.

Abstract

Galectin-1 (gal-1) is a 14-kDa laminin-binding galectin involved in several biologic events including regulation of cancer cell proliferation and adhesion to the matrix. In this study, we examined gal-1 expression in 30 human epithelial ovary carcinoma samples by Western and Northern blotting and by immunohistochemistry. Gal-1 mRNA levels were increased in more than 95% of the examined ovary carcinoma samples, compared with a wedge resection of a normal ovary. Immunohistochemical analysis of the samples demonstrated gal-1 expression in cancer epithelial cells from 17 of 30 samples, with a cytoplasmic pattern. Gal-1 immunostaining was significantly increased in the stroma associated with carcinoma cells compared with the normal, noninvaded stroma (p = 0.003). This pattern of expression was confirmed by examination of 12 other frozen epithelial ovary carcinomas, using in situ hybridization. Immunohistochemical staining of the specimens demonstrated colocalization of gal-1, laminin-1, and fibronectin. In vitro experiments were conducted to elucidate the potential biologic role of gal-1 in ovarian cancer progression. Gal-1 protein expression and release was detected in AZ364, SK-OV-3, and AZ224, but not in OVCAR-3, AZ419, and AZ382, human ovary carcinoma cell lines. Incubation of 84BR fibroblasts with conditioned media harvested from the ovary carcinoma cell lines induced an increased expression of gal-1 in the cultured fibroblasts in all cases except AZ419 and SK-OV-3. High concentrations of gal-1 (100 micro g/ml) induced significantly decreased cell proliferation in all cell lines, as defined by bromodeoxyuridine incorporation. Additionally, recombinant gal-1 induced a dose-dependent increase in in vitro adhesion of AZ224, SK-OV-3, and AZ382 cells to laminin-1; adhesion to fibronectin was increased by gal-1 in OVCAR-3, AZ224, and SK-OV-3. No effect was observed in the other cases. Our data contribute to define a role for gal-1 during the interactions between human ovary carcinoma cells and host fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Blotting, Northern
  • Blotting, Western
  • Cell Division
  • Dose-Response Relationship, Drug
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibronectins / metabolism*
  • Flow Cytometry
  • Galectin 1 / genetics
  • Galectin 1 / metabolism*
  • Galectin 1 / pharmacology
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Laminin / metabolism*
  • Neoplasm Staging
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / metabolism
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Tumor Cells, Cultured

Substances

  • Fibronectins
  • Galectin 1
  • Laminin
  • RNA, Messenger
  • laminin 1