Tumor control mechanism of galactoside-binding lectin in metastasis of urogenital cancer

半乳糖凝集素-3是一种存在于细胞内外环境的β-半乳糖苷结合蛋白家族成员，在多种癌细胞中过表达，并通过调节肿瘤增殖、血管生成和细胞凋亡与肿瘤进展和转移相关。前列腺癌方面，25 μM CDDP作用48小时后，66.3%的阴性前列腺癌细胞LNCap细胞出现DNA断裂，而表达galectin-3的LNCap细胞只有2.9%出现凋亡。300 μM etoposide作用48小时，48.3%的LNCap细胞出现凋亡，而表达galectin-3的LNCap细胞仅有15.4%出现凋亡。细胞内半乳糖凝集素-3可抑制线粒体从细胞核向细胞质易位后的损伤，从而抑制细胞色素c的释放和caspase-3的激活。半乳糖凝集素-3通过调节线粒体完整性、细胞色素c释放和caspase-3激活来抑制抗癌药物诱导的细胞凋亡。最近我们的微阵列研究揭示了garrectin -3在人肾细胞癌（RCC）中的过表达。半乳糖凝集素-3在肾切除术后的肾细胞癌中的表达水平明显高于相同标本的肾实质。用表达galectin-3的细胞上清液处理12小时后，约45%的CD8+ t细胞凋亡，而用siRNA减少galectin-3的细胞，只有15-18%的细胞凋亡。这些结果表明，半凝集素-3在RCC中高表达，细胞外的半凝集素-3诱导CD8+ t细胞凋亡。这些结果表明半乳糖凝集素-3调节抗癌药物诱导的前列腺癌细胞凋亡和RCC的抗癌免疫抑制。综上所述，半乳糖凝集素-3可能是前列腺癌化疗及RCC免疫逃逸的靶蛋白之一。

Galectin-3, a member of the β-galactoside binding protein family found in the intracellular and extracellular milieu, has overexpressed in a variety of cancer cells and has been shown to be correlated with tumor progression and metastasis through the regulation of tumor proliferation, angiogenesis, and apoptosis.Concerning the prostate cancer, after treatment with 25 μM CDDP for 48 hours, 66.3% of control LNCap cells which are garectiin-3 negative prostate cancer cell line showed DNA fragmentation, whereas only 2.9% of galectin-3 expressing LNCap cells were apoptotic. In the exposure with 300 μM etoposide for 48 hours, 48.3% of control LNCap cells were apoptotic, whereas only 15.4% of galectin-3 expressing LNCap were apoptotic. Intracellular galectin-3 inhibited mitochondrial damage after translocation from nuclei to cytoplasm, resulting inhibition of cytochrome c release and caspase-3 activation. Galectin-3 inhibited anticancer drug-induced apoptosis in the result of regulation of mitochondrial integrity, cytochrome c release, and caspase-3 activation.Recent our microarray studies have revealed garectin-3 overexpresses in human renal cell carcinoma (RCC). The expression level of galectin-3 in RCC obtained from nephrectomy was significantly higher than that in renal parenchyma obtained from same samples. After treatment with supernatant of garectin-3 expressing cells for 12 hours, approximately 45% of CD8+ T-cells were apoptotic, whereas in galectin-3 reduced cells by siRNA, only 15-18% of the cells were apoptotic. These result indicates that galectin-3 is highly expressed in RCC and extracellular garectin-3 induces apoptosis of CD8+ T-cells.These results suggest that galectin-3 regulated anticancer drug-induced apoptosis in prostate cancer and anti-cancer immune suppression in RCC. Taken together, it is suggested that galectin-3 is one of the target proteins for cancer chemotherapy in prostate cancer and immune escape of RCC.