Department of Pathology, Tianjin Medical University, Heping District Qixiangtai Road No. 22, Tianjin, 300070, People's Republic of China.
Med Oncol. 2012 Dec;29(5):3599-607. doi: 10.1007/s12032-012-0245-5. Epub 2012 May 5.
Vasculogenic mimicry (VM) refers to the unique ability of highly aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Hypoxia plays a pivotal role in the formation of VM. Hypoxia-induced Bcl-2 overexpression is observed in many types of tumors including melanoma, in which it is associated with tumorigenicity and angiogenesis. VE-cadherin, the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation, is also overexpressed in melanoma. Despite these connections, whether hypoxia induces VM formation via VE-cadherin regulation by Bcl-2 is not confirmed. We used human melanoma cells to upregulate or knockdown the expression of Bcl-2 to investigate the possible molecular mechanism of VM formation under hypoxia. Bcl-2 overexpression increased VE-cadherin expression and VM formation under normoxia, whereas Bcl-2 siRNA significantly decreased VE-cadherin expression and VM formation under hypoxia. We then demonstrated that Bcl-2 regulated VE-cadherin transcription activity by Western blot, three-dimensional cultures, reporter gene assay, and clinical analysis. Therefore, Bcl-2-dependent VE-cadherin overexpression may be an important mechanism by which hypoxia induces VM.
血管生成拟态（VM）是指高度侵袭性肿瘤细胞模仿胚胎血管生成网络模式的独特能力。缺氧在 VM 的形成中起着关键作用。在包括黑色素瘤在内的许多类型的肿瘤中都观察到缺氧诱导的 Bcl-2 过表达，它与肿瘤发生和血管生成有关。VE-钙黏蛋白是控制细胞连接和血管形成的主要内皮黏附分子，在黑色素瘤中也过表达。尽管存在这些联系，但缺氧是否通过 Bcl-2 调节 VE-钙黏蛋白来诱导 VM 形成尚未得到证实。我们使用人黑色素瘤细胞上调或敲低 Bcl-2 的表达，以研究缺氧下 VM 形成的可能分子机制。Bcl-2 过表达在常氧条件下增加了 VE-钙黏蛋白的表达和 VM 的形成，而 Bcl-2 siRNA 则显著降低了缺氧条件下 VE-钙黏蛋白的表达和 VM 的形成。然后，我们通过 Western blot、三维培养、报告基因检测和临床分析证明，Bcl-2 通过调节 VE-钙黏蛋白转录活性来发挥作用。因此，Bcl-2 依赖性 VE-钙黏蛋白过表达可能是缺氧诱导 VM 的一个重要机制。
