The tumor control mechanism of galectin-3 in urological cancer invasion and metastasis

Galectin-3是β-半乳糖苷结合的哺乳动物凝集素家族的一员，在多种肿瘤细胞中高水平表达，与肿瘤的侵袭、转移和细胞凋亡有关，但关于某一种肿瘤仍有一些相互矛盾的数据。到目前为止，在泌尿系肿瘤领域，关于Galectin-3与肿瘤侵袭的细胞凋亡方面的实验和临床证据报道很少。本研究采用RT-PCR和免疫印迹方法检测Galecin-3在肾癌细胞系和人肾细胞癌组织中的表达，探讨Galecin-3作为肿瘤标志物的临床意义和可能性。Galectin-3在所有肾癌细胞系中均有表达，人肾细胞癌组织中Galectin-3的表达显著高于正常肾组织(418.6±137.3 vs66.7±13.5，p=0.019)。特别是在有转移的病例中，其表达比例为…两者差异有统计学意义(p=0.035)，提示该比率可能成为影响转移的预后因素。同样，在转移病例中，与血管生成或TRAIL诱导的凋亡相关基因的表达与Galectin-3成正比。我们观察到，RT4细胞具有很低水平的固有活性Akt，并且对TRAIL敏感，而UM-UC-3和T24细胞具有较高的固有活性Alt水平，并且对TRAIL具有耐药。Galectin过表达细胞中活性Akt的表达水平高于野生型细胞，但两者Akt的总表达水平相似，提示Galectin-3与TRAIL耐药有关。50%Galectin-3被击倒的细胞表现出与PI3K抑制剂下调Akt活性的程度相同的程度，考虑到未来应用于临床，还需要进行一些生物调节，以寻找Galectin-3作为泌尿系肿瘤细胞凋亡诱导因子的可能性。较少

Galectin-3 is a member of the family of β-galactoside binding mammalian lectins that is expressed at elevated levels in a variety of neoplastic cell types and has been implicated in tumor invasion and metastatic process, and apoptosis, though there are still some conflicting data regarding a certain type of tumors. To date, in urological cancer field, few experimental and clinical evidences have been reported regarding galectin-3 and cancer invasion in terms of 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. 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 (418.6±137.3 vs 66.7±13.5, p=0.019). Especially in the case with metastasis, the expression ratio was … More significantly high (p=0.035), which suggested that ratio could become prognostic factor of metastasis. Similarly, in metastasis cases, the expressions of the genes associated with angiogenesis or TRAIL-induced apoptosis were elevated in proportion to that of galectin-3.We observed that RT4 cells had very low level of constitutively active Akt and were sensitive to TRAIL, while UM-UC-3 and T24 cells had higher level of constitutively active Alt and were resistant to TRAIL. The expression level of active Akt was higher in galectin-overexpressed cells than that in wild type cells, though total expression level of Akt were similar between these cells, implicating the relation of galectin-3 in TRAIL resistance. 50% Galectin-3 knocked down cells demonstrated the decrease of active Akt expression to the same extent as that down-regulated by PI3K inhibitors.Considering application to clinical field in future, some biological modulation will be required to find the possibility of galectin-3 as apoptosis inducing factor in urological cancers. Less