Van Den Brule F, et al reported that 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.
The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. LGALS1 may act as an autocrine negative growth factor that regulates cell proliferation.
Ligand, Cell adhesion molecule
Extracellular Matrix, Secreted
Walzel H, et al 2004 .
The detection of galectin-1 (gal-1) in pig granulosa cell lysates by immunoblotting and its cytosolic as well as membrane-associated localization prompted us to study its effects on cell proliferation and regulation of progesterone synthesis. The lectin stimulated the proliferation of granulosa cells from pig ovaries cultured in serum-free medium. Gal-1 inhibited the FSH stimulated progesterone synthesis of granulosa cells. This inhibitory effect was strongly reduced by the disaccharidic competitor lactose at 30 mM. The absence of inhibitory effects on dibutyryl-cAMP (db-cAMP), forskolin, and on pregnenolone-enhanced cellular progesterone synthesis suggests that gal-1interferes the receptor-dependent mechanism of FSH stimulated progesterone production. In FSH stimulated granulosa cells, Western blot analysis revealed the gal-1 mediated suppression of the cytochrome P450 dependent cholesterol side-chain cleavage enzyme (P450SCC) that catalyses the conversion of cholesterol to pregnenolone. In the presence of 30 mM lactose, the gal-1 reduced P450SCC expression was prevented. Strongly reduced mRNA levels were recorded for P450SCC and 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) when FSH stimulated granulosa cells were cultured in the presence of gal-1. We conclude that gal-1 exerts its inhibitory effect on steroidogenic activity of granulosa cells by interfering the hormone-receptor interaction resulting in decreased responses to FSH stimulation.
Expression regulated by
Granulosa, Luteal cells
The loss of luteal progesterone production in women is associated with a galectin switch via a2,6-sialylation of glycoconjugates. Nio-Kobayashi J 2014 et al.
Context: Luteal progesterone is fundamental for reproduction but the molecular regulation of the corpus luteum (CL) in women remains unclear. Galectin-1 and galectin-3 bind to the sugar chains on cells to control key biological processes including cell function and fate. Methods: The expression and localization of LGALS1 and LGALS3 was analyzed by quantitative PCR and histochemical analysis, with special reference to a2,6-sialylation of glycoconjugates, in carefully-dated human CL collected across the menstrual cycle and after exposure to hCG in vivo. The effects of hCG and prostaglandin E2 (PGE2) on the expression of galectins and an a2,6-sialyltransferase, ST6GAL1, in granulosa lutein cells were analyzed in vitro. Results: Galectin-1 was predominantly localized to healthy granulosa lutein cells and galectin-3 was localized to macrophages and regressing granulosa lutein cells. Acute exposure to luteotrophic hormones (hCG and PGE2) up-regulated LGALS1 expression (P<0.001). ST6GAL1, which catalyzes a2,6-sialylation to block galectin-1 binding, increased during luteolysis (P<0.05) as did LGALS3 (P<0.05). Luteotrophic hormones reduced ST6GAL1 and LGALS3 in vivo (P<0.05) and in vitro (P<0.001). There was an inverse correlation between the expression of ST6GAL1 and HSD3B1 (P<0.01), and a distinct cellular relationship among a2,6-sialylation, 3?HSD, and galectin expression. Conclusions: Galectin-1 is a luteotrophic factor whose binding is inhibited by a2,6-sialylation in the human CL during luteolysis. ST6GAL1 and galectin-3 expression is increased during luteolysis and associated with a loss of progesterone synthesis. Luteotrophic hormones differentially regulate galectin-1 and galectin-3/a2,6-sialylation in granulosa lutein cells, suggesting a novel galectin switch regulated by luteotrophic stimuli during luteolysis and luteal rescue.
Galectin-1 and galectin-3 in the corpus luteum of mice are differentially regulated by prolactin and prostaglandin F2a Nio-Kobayashi J et al. Galectin-1 and galectin-3, ?galactoside-binding lectins, are specifically expressed in the regressing corpus luteum (CL) of mice, however, their function remains unclear. In this study, we examined the effects of prolactin (PRL) and prostaglandin F(2a) (PGF(2a)), two main regulatory molecules of mouse CL function, on galectin expression. In situ hybridization analysis clearly demonstrated an initial increase of galectin-1 in the CL newly formed (CLN) after postpartum ovulation 48 h after compulsory weaning. This was accompanied by a decline in 3?hydroxysteroid dehydrogenase (3?HSD) and luteinizing hormone receptor (LH-R) expression, suggesting a withdrawal of PRL stimulation. At 72 h after the weaning, the expression of both galectins in CLN was remarkably increased, being associated with an intense expression of progesterone degradation enzyme (20a-HSD). Compulsory weaning did not significantly alter both galectin expression in the remaining CL of pregnancy (CLP), while PGF(2a) strongly up-regulated both galectin expression only in the remaining CLP which lacked LH-R in postpartum mice. Administration of Bromocriptine, an antagonist for PRL secretion, to non-pregnant cyclic mice induced an accumulation of galectin-1 -but not galectin-3- in all CL of various generations, and additional PRL treatment reduced its accumulation, suggesting a direct suppressive effect of PRL on galectin-1 expression. Although the function and regulatory mechanism of galectin in the CL is not fully understood, PGF(2a) is an excellent candidate which regulates galectin expression but its effect may be abolished by LH-R-mediated signal. PRL withdrawal seems to be necessary for an initiation of luteolysis and the following PGF(2a)-induced galectin expression.