Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Medical College, Shanghai Sixth People's Hospital of Shanghai Jiaotong University, No. 600 Yishan Road, Shanghai, 200233, China.
Pathol Oncol Res. 2010 Mar;16(1):111-7. doi: 10.1007/s12253-009-9198-1. Epub 2009 Sep 17.
Osteosarcoma cells can generate vasculogenic-like, patterned networks to obtain nutrients and oxygen, which mimic some function of endothelial-like cells and facilitate tumor malignant progress. These cells also express vascular endothelial-cadherin (VE-cadherin), which is generally accepted as a strictly endothelial-specific transmembrane protein. However, its role is still relatively obscure in osteosarcoma cells. So we inhibit the VE-cadherin gene expression with siRNA in osteosarcoma cells (MG63), and culture those cells in three-dimensional medium, containing Type I collagen or Matrigel, to observe the role of VE-cadherin. Western blotting analysis show that sequence-specific siRNA can significantly decrease the expression of VE-cadherin in MG63 cell. After knockdown of VE-cadherin, osteosarcoma cells can't induced angiogenic sprout and form osteosarcoma-generated, endothelial-like networks. Our data indicate that VE-cadherin may be a positive and specific regulator not only in angiogenesis, but also in vasculogenic mimicry of osteosarcoma cells. And it can be considered as a new prospective option in the combining treatment of aggressive tumor with highly vascularity, including osteosarcoma.
骨肉瘤细胞可以生成血管生成样的、有图案的网络来获取营养和氧气，这模拟了内皮样细胞的某些功能，并促进肿瘤的恶性进展。这些细胞还表达血管内皮钙黏蛋白 (VE-cadherin)，它通常被认为是一种严格的内皮特异性跨膜蛋白。然而，其在骨肉瘤细胞中的作用仍然相对模糊。因此，我们使用 siRNA 抑制骨肉瘤细胞 (MG63) 中的 VE-cadherin 基因表达，并在含有 I 型胶原或 Matrigel 的三维培养基中培养这些细胞，以观察 VE-cadherin 的作用。Western blot 分析表明，序列特异性 siRNA 可显著降低 MG63 细胞中 VE-cadherin 的表达。VE-cadherin 敲低后，骨肉瘤细胞不能诱导血管生成芽并形成骨肉瘤产生的、内皮样网络。我们的数据表明，VE-cadherin 不仅可能是血管生成的正向和特异性调节剂，而且可能是骨肉瘤细胞血管生成拟态的正向和特异性调节剂。它可以被认为是一种新的有前途的选择，用于联合治疗具有高度血管生成的侵袭性肿瘤，包括骨肉瘤。
