Vasculogenic mimicry persists during glioblastoma xenograft growth

Abstract

Background: Vasculogenic mimicry (VM) describes the functional plasticity of aggressive tumor cells to form newly recognized microcirculation, lined by tumor cells rather than endothelial cells, in solid tumors. The presence of VM in glioma is significantly associated with high tumor grade and poor prognosis. However, whether VM is a regular feature or only a temporary phenomenon during glioma growth is unknown. This study was designed to observe VM during the growth of subcutaneous and orthotopic xenograft glioma in Balb/c nude mice. Methods: The human glioblastoma cell line (U87) was used as xenografts in Balb/c nude mice models. The xenografts were obtained at different stages of tumor growth, and evaluated for VM and endothelium-dependent vessels by dual staining for endothelial marker CD34 and periodic acid-Schiff (PAS). Results: It was found that the PAS-positive patterns which were identified as VM were persistent during tumor growth of both subcutaneous and orthotropic xenografts. Further analysis showed that the microvessel density (MVD) of endothelium-dependent vessels was positively correlated with the tumor size of subcutaneous xenograft (r = 0.406, P = 0.009), while no significant correlation was found between VM density (VMD) and the tumor size (r = 0.107, P = 0.512). Furthermore, VMD was negatively correlated with MVD (r = −0.404, P = 0.010). Conclusion: The study results revealed that both VM and endothelium-dependent vessels coexist persistently during glioblastoma xenograft growth, indicating that VM may complement microcirculation in gliomas.

Keywords

• Angiogenesis
• glioma
• vasculogenic mimicry