Galectin-1: biphasic growth regulation of Leydig tumor cells

Abstract

Galectin-1 (Gal-1) is a widely expressed beta-galactoside-binding protein that exerts pleiotropic biological functions. To gain insight into the potential role of Gal-1 as a novel modulator of Leydig cells, we investigated its effect on the growth and death of MA-10 tumor Leydig cells. In this study, we identified cytoplasmic Gal-1 expression in these tumor cells by cytofluorometry. DNA fragmentation, caspase-3, -8, and -9 activation, loss of mitochondrial membrane potential (DeltaPsim), cytochrome c (Cyt c) release, and FasL expression suggested that relatively high concentrations of exogenously added recombinant Gal-1 (rGal-1) induced apoptosis by the mitochondrial and death receptor pathways. These pathways were independently activated, as the presence of the inhibitor of caspase-8 or -9 only partially prevented Gal-1-effect. On the contrary, low concentrations of Gal-1 significantly promoted cell proliferation, without inducing cell death. Importantly, the presence of the disaccharide lactose prevented Gal-1 effects, suggesting the involvement of the carbohydrate recognition domain (CRD). This study provides strong evidence that Gal-1 is a novel biphasic regulator of Leydig tumor cell number, suggesting a novel role for Gal-1 in the reproductive physiopathology.

Intracellular galectins in cancer cells: Potential new targets for therapy

“…Given their role in apoptosis, it is not surprising that galectins play a central role in the control of cell proliferation in tumors. This has been well documented in the case of galectin-1, which reduces proliferation of B-cell lymphomas, neuroblastoma and LnCap prostate cancer cells while it increases cell division of glioma, cervical, ovarian and pancreatic cancer cells (12,51,58,61,62,64,93). A similar case exists for galectin-3, which displays, once more dual functionalities in cell proliferation.…”

“…Moreover, its presence is also seen in the cytosol of neuroblastoma and small cell lung carcinoma tissues, testicular interstitial and cervical carcinoma cell lines (MA-10 and HeLa), hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinoma tissues, human melanoma cell lines (A375 and A2058) and colorectal cancer tissues including adenomas, carcinomas and metastases from patients (9,(11)(12)(13)(14)(15). Although fewer studies have been conducted on galectin-2, the available data indicate its presence in the nucleus of genetically engineered human colon cancer cells that have ectopic stable expression (16) in addition to gastric carcinoma tissues, epidermoid carcinoma, osteosarcoma and glioblastoma cell lines (A-431, U-2 OS and U-251MG) (17,18).…”

“…A positive correlation between the expression of galectin-1 and -3 and malignant transformation has been established using different cellular models (49)(50)(51) (12,(58)(59)(60)(61). Conversely, it reduces apoptosis in gliomas, cervical and lung cancer (62)(63)(64).…”

The oncofetal Thomsen–Friedenreich carbohydrate antigen in cancer progression

“…Down regulation of galectin-3 expression by antisense technique in human breast carcinoma MDA-MB-435 cells leads to significant suppression of the tumour growth in soft agar and in nude mice [74]. Recombinant galectin-1 promotes proliferation of MA-10 Leydig tumour cells [75] and rat hepatic stellate cells [73] at low concentrations but shows inhibition of cell proliferation at higher concentrations (>20 ug/ml) on trophoblast tumour cells [69] and (>12.5 ug/ml) on neuroblastoma [76]. In all those proliferation studies on galectins, however, the galectin binding ligands are not characterized hence the level of involvement of the TF structure in these galectinmediated effects on cell growth remains to be determined.…”

Expressão de Galectinas-1 e 3 em Neoplasias Mieloproliferativas

“…Foi observado que em células tumorais de Leydig as altas concentrações de Gal-1 são as responsáveis diretas pela inibição da proliferação celular enquanto que baixas concentrações induzem a mitose das células (BIRON, et al;2006). Nessa mesma linha de pensamento células de linhagem de câncer de próstata transfectadas com o vetor contendo o gene LGALS1, apresentaram diminuição da proliferação e aumento da taxa de apoptose (ELLERHORST et al;.…”