Department of Urology, The Second Affiliated Hospital of Shantou University Medical College, China.
Department of Urology, The First Affiliated Hospital of Shantou University Medical College, China.
Biomed Res Int. 2019 Jul 21;2019:7259691. doi: 10.1155/2019/7259691. eCollection 2019.
Vasculogenic mimicry (VM), the novel approach for tumor cells to obtain blood supply, was reported to be involved in antiangiogenic resistance and poor prognosis in renal cell carcinoma (RCC). However, the molecular mechanisms underlying VM formed by RCC cells are still not clearly depicted. In the present study, we found that OS-RC-2 acquired the VM forming ability accompanied with the increased expressions of Vimentin and AXL and decreased expression of E-Cadherin by CoCl treatment. Downregulation of Vimentin by siRNA severely impaired the capability of OS-RC-2 and 786-O to form VM structures induced by cell hypoxia in vitro. Moreover, knockdown of Vimentin inhibited cell migration and invasion, which could be prompted by hypoxia induction in RCC cells. In our clear cell RCC tissues, we found that VM was positively correlated with Vimentin overexpression and both predicted poor prognosis. In conclusion, Vimentin plays an important role in hypoxia induced VM formation of RCC cells and targeted Vimentin might be beneficial for RCC therapy.
血管生成拟态（VM）是肿瘤细胞获得血液供应的新途径，据报道，它与肾细胞癌（RCC）中的抗血管生成耐药和预后不良有关。然而，RCC 细胞形成的 VM 的分子机制尚不清楚。在本研究中，我们发现 CoCl 处理后 OS-RC-2 获得了形成 VM 的能力，同时 Vimentin 和 AXL 的表达增加，E-Cadherin 的表达减少。通过 siRNA 下调 Vimentin 可严重损害 OS-RC-2 和 786-O 在体外细胞缺氧诱导下形成 VM 结构的能力。此外，Vimentin 的敲低抑制了 RCC 细胞缺氧诱导的迁移和侵袭能力。在我们的透明细胞 RCC 组织中，我们发现 VM 与 Vimentin 过表达呈正相关，两者均预示着预后不良。总之，Vimentin 在缺氧诱导的 RCC 细胞 VM 形成中起重要作用，靶向 Vimentin 可能有益于 RCC 的治疗。
