Nojima Hiroshi, Ohba Yusuke, Kita Yasuyuki
Department of Molecular Genetics, Research Institute for Microbial Diseases, Graduate School of Pharmaceutical Science, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Curr Drug Saf. 2007 Sep;2(3):204-11. doi: 10.2174/157488607781668837.
Despite considerable research, metastasis remains a major challenge in the clinical management of cancer. Recent reports show that abnormally augmented expression of Cx26 is responsible for the enhanced spontaneous metastasis of mouse BL6 melanoma cells. The function of Cx26 appears to be responsible for this phenotype since exogenous expression of a dominant-negative form of Cx26 and oleamide derivatives called MI-18 and MI-22 that specifically inhibit Cx26-mediated gap junction-mediated intercellular communications (GJIC) prevent the spontaneous metastasis of BL6 cells. As expected from their structural similarity to oleic acid (the major component of olive oil), both MI-18 and MI-22 are safe drugs; nonetheless, they are potent inhibitors of the spontaneous metastasis of BL6 mouse melanoma cells. Thus, they are a novel prototype of an anti-metastasis drug that has minimal side effects. While the primary tumors do not necessarily show strong Cx26-immunostaining signals, pronounced Cx26 expression is detected in the highly invasive tumor regions; it is also more frequently observed in metastasized tumors. Thus, Cx26 expression may be useful as a prognostic tool that can predict the existence of highly metastatic cancer cells in clinical samples.
尽管进行了大量研究，但转移仍然是癌症临床治疗中的一个主要挑战。最近的报告表明，Cx26表达异常增强是小鼠BL6黑色素瘤细胞自发转移增强的原因。Cx26的功能似乎是造成这种表型的原因，因为外源性表达一种显性负性形式的Cx26以及名为MI-18和MI-22的油酸酰胺衍生物（它们能特异性抑制Cx26介导的间隙连接介导的细胞间通讯（GJIC））可阻止BL6细胞的自发转移。正如预期的那样，由于MI-18和MI-22与油酸（橄榄油的主要成分）结构相似，它们都是安全的药物；尽管如此，它们却是BL6小鼠黑色素瘤细胞自发转移的有效抑制剂。因此，它们是一种副作用极小的抗转移药物的新型原型。虽然原发性肿瘤不一定显示出强烈的Cx26免疫染色信号，但在高侵袭性肿瘤区域可检测到明显的Cx26表达；在转移瘤中也更频繁地观察到这种情况。因此，Cx26表达可能作为一种预后工具，用于预测临床样本中高转移性癌细胞的存在。
