The role of galectin-3 in human renal cell cancer cells

半乳糖凝集素-3是半乳糖凝集素基因家族的成员，其在多种肿瘤细胞类型中以升高的水平表达，并且与细胞生长、细胞粘附过程、细胞增殖、转化、转移和凋亡相关。本研究采用RT-PCR和Western blot方法检测半乳糖凝集素-3（galecin-3）在肾癌细胞系和肾癌组织中的表达，探讨其临床意义和作为肿瘤标志物的可能性。我们还研究了其对T细胞或NK细胞活化的影响。半乳糖凝集素-3在我们使用的每个肾细胞癌细胞系中均被鉴定出表达，并且在人肾细胞癌组织中的表达显著高于正常肾组织。特别是在有转移的病例中，其表达率显著增高（p=0.035），提示该比值可作为转移的预后因子。我们从人肾癌组织中提取CD 8阳性T细胞，并通过流式细胞术研究galectin-3诱导细胞凋亡的作用。Galectin-3通过与CD 8阳性T细胞结合而显著诱导细胞凋亡（p=0.039），由此我们得出结论，Galectin-3可能参与了肾细胞癌的所谓“逃逸”免疫系统。我们还建立了小鼠肾细胞癌模型和转移模型的Renca细胞（阳性和阴性galectin-3表达），并研究了抗血管生成和抗肿瘤作用。这些结果将很快公布。阐明galectin-3在血管生成或凋亡中的作用，有助于了解肾癌对各种治疗耐药的机制。在未来，我们计划将这些成果扩展到肾细胞癌的基因治疗。

Galectin-3 is a member of the galectin gene family that is expressed at elevated levels in a variety of neoplastic cell types and has been associated with cell growth, cellular adhesion process, cell proliferation, transformation, metastasis, and apoptosis. We studied the expression of galecin-3 in renal cell carcinoma cell lines and human renal cell carcinoma tissues by RT-PCR and western blot analysis, and investigated the clinical significance and the possibility as a tumor marker. We also investigated its effect on T cell or NK cell activation. The expression of galectin-3 was identified in every renal cell carcinoma cell line we employed and was significantly higher in human renal cell carcinoma tissues than normal kidney tissues. Especially in the case with metastasis, the expression ratio was significantly high (p=0.035), which suggested that ratio could become prognostic factor of metastasis. We extracted CD8 positive T cells from human renal cell carcinoma tissues and investigated the effect of galectin-3 induced apoptosis in the cells by flow cytometry. Galectin-3 significantly induced apoptosis (p=0.039) by binding to the CD8 positive T cells, from which we concluded that galectin-3 might be involved in what is called ‘escape' from immune system of renal cell carcinoma. We have also constructed mice RCC models and metastasis models by employing Renca cells (positive and negative galectin-3 expression) and investigated anti-angiogenesis and anti-tumor effect. These results will be published shortly. To clarify the role of galectin-3 in angiogenesis or apoptosis may lead to understanding mechanism of resistance of renal cell carcinoma to various kinds of therapies. In future we plan to expand these achievements into gene therapy for renal cell carcinoma.