Dual activities of galectin-3 in human prostate cancer:: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3
Dual activities of galectin-3 in human prostate cancer:: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3
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DOI：
10.1038/sj.onc.1207997
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发表时间：
2004-09-30
期刊：
影响因子：
8
通讯作者：
van den Brûle, F
中科院分区：
文献类型：
--
作者：
Califice, S;Castronovo, V;van den Brûle, F
Galectin-3是一种多功能凝集素，参与肿瘤进展过程。以往的研究表明，半乳糖凝集素-3在人前列腺癌细胞中的胞浆表达和核排斥与疾病的进展有关。在这项研究中，我们研究了Galectin-3在细胞核或胞浆中表达时的生物学作用。LNCaP是一种Galectin-3阴性的人前列腺癌细胞系，用来产生在细胞核或胞浆中表达Galectin-3的转基因细胞。未观察到细胞形态、增殖、粘附层粘连蛋白-1或雄激素依赖性的改变。胞质Galectin-3诱导的Matrigel侵袭、非贴壁生长、体内肿瘤生长和血管生成显著增加，诱导的细胞凋亡减少。令人惊讶的是，核Galectin-3以相反的方式影响了这些参数，具有整体的抗肿瘤活性。因此，我们的研究表明，Galectin-3根据其细胞定位而发挥相反的生物学活性：核Galectin-3发挥抗肿瘤功能，细胞质Galectin-3促进肿瘤进展。
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.