Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3.
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.
Metastasis Research Laboratory, Experimental Cancer Research Center, University of Liège, Belgium.
Stéphane
S
Califice
Vincent
V
Castronovo
Marc
M
Bracke
Frédéric
F
van den Brûle
D000728:Androgens / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D002642:Chick Embryo; D003593:Cytoplasm / Q000378:metabolism*; D017931:DNA Primers; D037502:Galectin 3 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology*
D000728:Androgens; D017931:DNA Primers; D037502:Galectin 3