Este artículo es de Acceso Abierto y puede ser descargado en su versión final desde nuestro repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor


Galectin-1 (Gal-1) is a widely expressed β-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 (ΔΨ m), 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. © Copyright 2006 Oxford University Press.


Documento: Artículo
Título:Galectin-1: Biphasic growth regulation of Leydig tumor cells
Autor:Biron, V.A.; Iglesias, M.; Troncoso, M.F.; Besio-Moreno, M.; Patrignani, Z.J.; Pignataro, O.P.; Wolfenstein-Todel, C.
Filiación:Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina
Laboratorio de Endocrinología Molecular y Transducción de Señales, Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II, 1428 Buenos Aires, Argentina
Palabras clave:Apoptosis; Galectin-1; Leydig cells; Proliferation; caspase 3; caspase 8; caspase 8 inhibitor; caspase 9; caspase 9 inhibitor; cytochrome c; death receptor; disaccharide; DNA fragment; FAS ligand; galectin 1; lactose; animal cell; apoptosis; article; carbohydrate analysis; cell growth; cell membrane potential; cell proliferation; controlled study; cytofluorometry; enzyme activation; growth regulation; Leydig cell; Leydig cell tumor; male; mitochondrial membrane; mouse; nonhuman; pathophysiology; priority journal; protein determination; protein expression; protein function; protein secretion; Cell Line, Tumor; Cell Proliferation; Cytoplasm; DNA Fragmentation; Dose-Response Relationship, Drug; Galectin 1; Gene Expression Regulation, Neoplastic; Humans; Lactose; Leydig Cells; Male; Membrane Potentials; Mitochondria; Neoplasm Proteins; Sertoli-Leydig Cell Tumor; Testicular Neoplasms
Página de inicio:810
Página de fin:821
Título revista:Glycobiology
Título revista abreviado:Glycobiology
CAS:caspase 3, 169592-56-7; caspase 9, 180189-96-2; cytochrome c, 9007-43-6, 9064-84-0; galectin 1, 258495-34-0; lactose, 10039-26-6, 16984-38-6, 63-42-3, 64044-51-5; Galectin 1; Lactose, 63-42-3; Neoplasm Proteins


  • Adams, L., Scott, G.K., Weinberg, C.S., Biphasic modulation of cell growth by recombinant human galectin-1 (1996) Biochim. Biophys. Acta, 1312, pp. 137-144
  • Ahmed, H., Fink, N.E., Pohl, J., Vasta, G.R., Galectin-1 from bovine spleen: Biochemical characterization, carbohydrate specificity and tissue-specific isoform profiles (1996) J. Biochem., 120, pp. 1007-1019
  • Akazawa, C., Nakamura, Y., Sango, K., Horie, H., Kohsaka, S., Distribution of the galectin-1 mRNA in the rat nervous system: Its transient upregulation in rat facial motor neurons after facial nerve axotomy (2004) Neuroscience, 125, pp. 171-178
  • Ascoli, M., Characterization of several clonal lines of cultured Leydig tumor cells: Gonadotropin receptors and steroidogenic responses (1981) Endocrinology, 108, pp. 88-95
  • Barondes, S.H., Cooper, D.N.W., Gitt, M.A., Leffler, H., Galectins. Structure and function of a large family of animal lectins (1994) J. Biol. Chem., 269, pp. 20807-20810
  • Baum, L.G., Pang, M., Perillo, N.L., Wu, T., Delegeane, A., Uittenbogaart, C.H., Fukuda, M., Seilhamer, J.J., Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells (1995) J. Exp. Med., 181, pp. 877-887
  • Camby, I., Belot, N., Rorive, S., Lefranc, F., Maurage, C.A., Lahm, H., Kaltner, H., Kiss, R., Galectins are differentially expressed in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas, and significantly modulate tumor astrocyte migration (2001) Brain Pathol., 11, pp. 12-26
  • Cho, M., Cummings, R.D., Galectin-1, a β-galactoside-binding lectin in Chinese hamster ovary cells (1995) J. Biol. Chem., 270, pp. 5198-5206
  • Choufani, G., Nagy, N., Saussez, S., Marchant, H., Bisschop, P., Burchert, M., Danguy, A., Gabius, H.J., The levels of expression of galectin-1, galectin-3, and the Thomsen-Friedenreich antigen and their binding sites decrease as clinical aggressiveness increases in head and neck cancers (1999) Cancer, 86, pp. 2353-2363. , and others
  • Cooper, D.N.W., Barondes, S.H., Evidence for export of a muscle lectin from cytosol to extracellular matrix and for a novel secretory mechanism (1990) J. Cell Biol., 110, pp. 1681-1691
  • Couraud, P.O., Casentini-Borocz, D., Bringman, T.S., Griffith, J., McGrogan, M., Nedwin, G.E., Molecular cloning, characterization and expression of a human 14-kDa lectin (1989) J. Biol. Chem., 264, pp. 1310-1316
  • Dettin, L., Rubinstein, N., Aoki, A., Rabinovich, G.A., Maldonado, C.A., Regulated expression and ultrastructural localization of galectin-1, a proapoptotic β-galactoside-binding lectin, during spermatogenesis in rat testis (2003) Biol. Reprod., 68, pp. 51-59
  • Ellerhorst, J., Nguyen, T., Cooper, D.N.W., Estrov, Y., Lotan, D., Lotan, R., Induction of differentiation and apoptosis in the prostate cancer cell line LNCaP by sodium butyrate and galectin-1 (1999) Int. J. Oncol., 14, pp. 225-232
  • Fautsch, M.P., Silva, A.O., Johnson, D.H., Carbohydrate binding proteins galectin-1 and galectin-3 in human trabecular meshwork (2003) Exp. Eye Res., 77, pp. 11-16
  • Gao, H.B., Tong, M.H., Hu, Y.Q., You, H.Y., Gou, Q.S., Ge, R.S., Hardy, M.P., Mechanism of glucocorticoid-induced Leydig cell apoptosis (2003) Mol. Cell Endocrinol., 199, pp. 153-163
  • Grataroli, R., Vindrieux, D., Gougeon, A., Benahmed, M., Expression of tumor necrosis factor-α-related apoptosis-inducing ligand and its receptors in rat testis during development (2002) Biol. Reprod., 66, pp. 1707-1715
  • Green, D.R., Kroemer, G., The pathophysiology of mitochondrial cell death (2004) Science, 305, pp. 626-629
  • Green, D.R., Reed, J.C., Mitochondria and apoptosis (1998) Science, 281, pp. 1309-1312
  • Hahn, H.P., Pang, M., He, J., Hernandez, J.D., Yang, R.Y., Li, L.Y., Wang, X., Baum, L.G., Galectin-1 induces nuclear translocation of endonuclease G in caspase- and cytochrome c-independent T cell death (2004) Cell Death Differ., 11, pp. 1277-1286
  • Hengartner, M.O., The biochemistry of apoptosis (2000) Nature, 407, pp. 770-776
  • Hirabayashi, J., Kasai, K., Human placenta beta-galactoside-binding lectin. Purification and some properties (1984) Biochem. Biophys. Res. Commun., 122, pp. 938-944
  • Hittelet, A., Legendre, H., Nagy, N., Bronckart, Y., Pector, J.C., Salmon, I., Yeaton, P., Camby, I., Upregulation of galectins-1 and -3 in human colon cancer and their role in regulating cell migration (2003) Int. J. Cancer., 103, pp. 370-379
  • Iglesias, M.M., Rabinovich, G.A., Ambrosio, A.L., Castagna, L.F., Sotomayor, C.E., Wolfenstein-Todel, C., Galectin-1 from ovine placenta. Amino-acid sequence, physicochemical properties and implications in T-cell death (1998) Eur. J. Biochem., 252, pp. 400-407
  • Iglesias, M.M., Rabinovich, G.A., Ambrosio, A.L., Castagna, L.F., Sotomayor, C.E., Wolfenstein-Todel, C., Purification of galectin-3 from ovine placenta: Developmentally regulated expression and immunological relevance (1998) Glycobiology, 8, pp. 59-65
  • Jang, M.H., Shin, M.C., Shin, H.S., Kim, K.H., Park, H.J., Kim, E.H., Kim, C.J., Alcohol induces apoptosis in TM3 mouse Leydig cells via bax-dependent caspase-3 activation (2002) Eur. J. Pharmacol., 449, pp. 39-45
  • Kumi-Diaka, J., Nguyen, V., Butler, A., Cytotoxic potential of the phytochemical genistein isoflavone (4′,5′,7-trihydroxyisoflavone) and certain environmental chemical compounds on testicular cells (1999) Biol. Cell, 91, pp. 515-523
  • Liu, F.T., Rabinovich, G.A., Galectins as modulators of tumour progression (2005) Nat. Rev., 5, pp. 29-41
  • Martínez, V.G., Pellizari, E.H., Díaz, E.S., Cigorraga, S.B., Lustig, L., Denduchis, B., Wolfenstein-Todel, C., Iglesias, M.M., Galectin-1, a cell adhesion modulator, induces apoptosis of rat Leydig cells in vitro (2004) Glycobiology, 14, pp. 127-137
  • Moiseeva, E.P., Javed, Q., Spring, E.L., de Bono, D.P., Galectin 1 is involved in vascular smooth muscle cell proliferation (2000) Cardiovasc. Res., 45, pp. 493-502
  • Moiseeva, E.P., Spring, E.L., Baron, J.H., de Bono, D.P., Galectin-1 modulates attachment, spreading and migration of cultured vascular smooth muscle cells via interactions with cellular receptors and components of extracellular matrix (1999) J. Vasc. Res., 36, pp. 47-58
  • Moiseeva, E.P., Williams, B., Goodall, A.H., Samani, N.J., Galectin-1 interacts with β1-subunit of integrin (2003) Biochem. Biophys. Res. Commun., 310, pp. 1010-1016
  • Mor, G., Straszewski, S., Kamsteeg, M., Role of the Fas-Fas ligand system in female reproductive organs: Survival and apoptosis (2002) Biochem. Pharmacol., 64, pp. 1305-1315
  • Nguyen, J.T., Evans, D.P., Galvan, M., Pace, K.E., Leitenberg, D., Bui, T.N., Baum, L.G., CD45 modulates galectin-1-induced T cell death: Regulation by expression of core 2 O-glycans (2001) J. Immunol., 167, pp. 5697-5707
  • Nicoletti, I., Migliorati, G., Pagliacci, M.C., Grignani, F., Riccardi, C.A., A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry (1991) J. Immunol. Methods, 139, pp. 271-279
  • Paz, A., Haklai, R., Elad-Sfadia, G., Ballan, E., Kloog, Y., Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation (2001) Oncogene, 20, pp. 7486-7493
  • Perillo, N.L., Pace, K.E., Seihamer, J.J., Baum, L.G., Apoptosis of T cells mediated by galectin-1 (1995) Nature, 378, pp. 736-739
  • Perillo, N.L., Uittenbogaart, C.H., Nguyen, J.T., Baum, L.G., Galectin-1, an endogenous lectin produced by thymic cells, induces apoptosis of human thymocytes (1997) J. Exp. Med., 185, pp. 1851-1858
  • Pignataro, O.P., Ascoli, M., Epidermal growth factor increases the labeling of phosphatidilinositol-3,4-biphosphate in MA-10 Leydig tumor cells (1990) J. Biol. Chem., 265, pp. 1718-1723
  • Rabinovich, G.A., Alonso, C.R., Sotomayor, C.E., Durand, S., Bocco, J.L., Riera, C.M., Molecular mechanisms implicated in galectin-1 - Induced apoptosis: Activation of the AP-1 transcription factor and downregulation of Bcl-2 (2000) Cell Death Differ., 7, pp. 747-753
  • Rabinovich, G.A., Daly, G., Dreja, H., Tailor, H., Riera, C.M., Hirabayashi, J., Chernajovsky, Y., Recombinant galectin-1 and its genetic delivery suppress collagen-induced arthritis via T cell apoptosis (1999) J. Exp. Med., 190, pp. 385-397
  • Rabinovich, G.A., Iglesias, M.M., Modesti, N.M., Castagna, L.F., Wolfenstein-Todel, C., Riera, C.M., Sotomayor, C.E., Activated rat macrophages produce a galectin-1-like protein that induces apoptosis of T cells: Biochemical and functional characterization (1998) J. Immunol., 160, pp. 4831-4840
  • Ramnath, H.I., Peterson, S., Michael, A.E., Stocco, D.M., Cooke, B.A., Modulation of steroidogenesis by chloride ions in MA-10 mouse tumor Leydig cells: Roles of calcium, protein synthesis, and the steroidogenic acute regulatory protein (1997) Endocrinology, 138, pp. 2308-2314
  • Rubinstein, N., Alvarez, M., Zwirner, N.W., Toscano, M.A., Ilarregui, J.M., Bravo, A., Mordoh, J., Rabinovich, G.A., Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection: A potential mechanism of tumor-immune privilege (2004) Cancer Cell, 5, pp. 241-251
  • Sánchez-Alcázar, J.A., Ault, J.G., Khodjakov, A., Scheider, E., Increased mitochondrial cytochrome c levels and mitochondrial hyperpolarization precede camptothecin-induced apoptosis in Jurkat cells (2000) Cell Death Differ., 7, pp. 1090-1100
  • Sasaki, T., Hirabayashi, J., Manya, H., Kasai, K., Endo, T., Galectin-1 induces astrocyte differentiation, which leads to production of brain-derived neutrophic factor (2004) Glycobiology, 14, pp. 357-363
  • Seelenmeyer, C., Wegehingel, S., Tews, I., Kunzler, M., Aebi, M., Nickel, W., Cell surface counter receptors are essential components of the unconventional export machinery of galectin-1 (2005) J. Cell Biol., 171, pp. 373-381
  • Stupack, D.G., Puente, X.S., Boutsaboualoy, S., Storgard, C.M., Cheresh, D.A., Apoptosis of adherent cells by recruitment of caspasa-8 to unligated integrins (2001) J. Cell Biol., 155, pp. 459-470
  • Taylor, M.F., de Boer-Brouwer, M., Woolveridge, I., Teerd, K.J., Morris, I.D., Leydig cell apoptosis after administration of ethane dimethanesulfonate to the adult male rat is a Fas-mediated process (1999) Endocrinology, 140, pp. 3797-3804
  • Van den Brule, F., Califice, S., Castronovo, V., Expression of galectins in cancer. A critical review (2004) Glycoconj. J., 19, pp. 537-542
  • Van den Brule, F., Califice, S., Garnier, F., Fernandez, P.L., Berchuck, A., Castronovo, V., 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 (2003) Lab. Invest., 83, pp. 377-386
  • Vas, V., Fajka-Boja, R., Ion, G., Dudics, V., Monostori, E., Uher, F., Biphasic effect of recombinant galectin-1 on the growth and death of early hematopoietic cells (2005) Stem Cells, 23, pp. 279-287
  • Vyakarnam, A., Dagher, S.F., Wang, J.L., Patterson, R.J., Evidence for a role for galectin-1 in pre-mRNA splicing (1997) Mol. Cell Biol., 17, pp. 4730-4737
  • Wells, V., Davies, D., Mallucci, L., Cell cycle arrest and induction of apoptosis by β galactoside binding protein (βGBP) in human mammary cancer cells. A potential new approach to cancer control (1999) Eur. J. Cancer, 35, pp. 978-983
  • Wollina, U., Schreiber, G., Görnig, M., Feldrappe, S., Burchert, M., Gabius, H.J., Sertoli cell expression of galectin-1 and -3 and accessible binding sites in normal human testis and Sertoli cell only syndrome (1999) Histol Histopathol., 14, pp. 779-784
  • Xu, X.C., el-Naggar, A.K., Lotan, R., Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications (1995) Am. J. Pathol., 147, pp. 815-822
  • Yamaoka, K., Mishima, K., Nagashima, Y., Asai, A., Sanai, Y., Kirino, T., Expression of galectin-1 mRNA correlates with the malignant potential of human gliomas and expression of anti-sense galectin-1 inhibits the growth of 9 glioma cells (2000) J. Neurosci., 59, pp. 722-730


---------- APA ----------
Biron, V.A., Iglesias, M., Troncoso, M.F., Besio-Moreno, M., Patrignani, Z.J., Pignataro, O.P. & Wolfenstein-Todel, C. (2006) . Galectin-1: Biphasic growth regulation of Leydig tumor cells. Glycobiology, 16(9), 810-821.
---------- CHICAGO ----------
Biron, V.A., Iglesias, M., Troncoso, M.F., Besio-Moreno, M., Patrignani, Z.J., Pignataro, O.P., et al. "Galectin-1: Biphasic growth regulation of Leydig tumor cells" . Glycobiology 16, no. 9 (2006) : 810-821.
---------- MLA ----------
Biron, V.A., Iglesias, M., Troncoso, M.F., Besio-Moreno, M., Patrignani, Z.J., Pignataro, O.P., et al. "Galectin-1: Biphasic growth regulation of Leydig tumor cells" . Glycobiology, vol. 16, no. 9, 2006, pp. 810-821.
---------- VANCOUVER ----------
Biron, V.A., Iglesias, M., Troncoso, M.F., Besio-Moreno, M., Patrignani, Z.J., Pignataro, O.P., et al. Galectin-1: Biphasic growth regulation of Leydig tumor cells. Glycobiology. 2006;16(9):810-821.