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.
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.
van den Brûle
Frédéric
F
Metastasis Research Laboratory, University of Liège, Liège, Belgium. f.vanderbrule@ulg.ac.be
Califice
Stéphane
S
Garnier
Frédérique
F
Fernandez
Pedro L
PL
Berchuck
Andrew
A
Castronovo
Vincent
V
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism*; D005434:Flow Cytometry; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007797:Laminin / Q000378:metabolism*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D037483:Galectin 1; D007797:Laminin; D012333:RNA, Messenger; C121346:laminin 1