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Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3

Abstract

Galectin-3, a multifunctional lectin, is involved during cancer progression. Previous observations showed that both cytosolic expression and nuclear exclusion of galectin-3 in human prostate cancer cells were associated to progression of the disease. In this study, we examined the biological roles of galectin-3 when expressed either in the nucleus or in the cytosol. LNCaP, a galectin-3-negative human prostate cancer cell line, was used to generate transfectants expressing galectin-3 either in the nucleus or in the cytosol. No changes in cell morphology, proliferation, attachment to laminin-1 or androgen dependency were observed. Cytoplasmic galectin-3 induced significantly increased Matrigel invasion, anchorage-independent growth and in vivo tumor growth and angiogenesis, and decreased inducible apoptosis. Surprisingly, nuclear galectin-3 affected these parameters in an opposite fashion with an overall antitumoral activity. Thus, our study demonstrates that galectin-3 exerts opposite biological activities according to its cellular localization: nuclear galectin-3 plays antitumor functions and cytoplasmic galectin-3 promotes tumor progression.

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Acknowledgements

We thank Fu-Tong Liu and Ri-Yao Yang (UC Davis, Sacramento, CA, USA) for the pEF1-galec3-neo plasmid, Françoise Rentier for expert advices in cloning strategy, Rosita Winkler and David Waltregny, for fruitful discussions, Rita Colman and Daan Vandekerckhove for performing the chick heart invasion assays, and Pascale Heneaux, Naïma Maloujahmoum, Sabine Thonard, Jacques Foguenne and Guy Roland for expert technical assistance. Stéphane Califice is the recipient of a Télévie Grant, and Frédéric van den Brûle is a Senior Research Associate of the National Fund for Scientific Research, Belgium. This work has been partially supported by the National Fund for Scientific Research, the Interuniversity Attraction Pole Program, the Association Sportive contre le Cancer, Télévie and the Léon Frédéricq Foundation (Belgium).

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Correspondence to Frédéric van den Brûle.

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Califice, S., Castronovo, V., Bracke, M. et al. Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3. Oncogene 23, 7527–7536 (2004). https://doi.org/10.1038/sj.onc.1207997

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