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

Abstract

SUMMARY: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 ϭ 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 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. (Lab Invest 2003, 83:377-386).

Increased expression of galectin-1 is associated with human oral squamous cell carcinoma development

“…Gal-1 was found overexpressed in hypopharyngeal and laryngeal squamous cell carcinomas (9). It also increased the adhesion of prostate cancer cells and ovarian cancer cells to extracellular matrix (22). Exogenous Gal-1 was proved to enhance the locomotivity of malignant glioma cells in vitro (23).…”

Expression of immune checkpoint molecules in endometrial carcinoma

“…Galectin-1 and galectin-3 upregulation has previously been demonstrated in numerous tumors, including bladder cancer (31,32), head and neck squamous cell carcinoma (33) and ovarian cancer (34,35). Numerous studies have detected galectin-1 and galectin-3 expression in endometrial carcinoma, although the results have been conflicting (4,36).…”

Galectin-1 Interacts with the α5β1 Fibronectin Receptor to Restrict Carcinoma Cell Growth via Induction of p21 and p27

“…Its widespread differential expression in malignant cells and their non-transformed counterparts raises the possibility that Gal-1 also functions as a modulator of proliferation in other cell types, such as epithelial cells. Indeed, growth inhibition of tumor cells by Gal-1 has been reported (10,11). Of note, these growth effects were unaffected by the presence of a glycan inhibitor (9) or not specified with respect to glycan inhibitors (11), whereas the proapoptotic action of galectins on activated T-cells clearly depended on ␤-galactoside-specific binding (12).…”