Vasculogenic mimicry: a novel target for glioma therapy

Abstract

Anti-angiogenic therapy has shown promising but insufficient efficacy on gliomas. Recent studies suggest that vasculogenic mimicry (VM), or the formation of non-endothelial, tumor-cell-lined microvascular channels, occurs in aggressive tumors, including gliomas. There is also evidence of a physiological connection between the endothelial-lined vasculature and VM channels. Tumor cells, by virtue of their high plasticity, can form vessel-like structures themselves, which may function as blood supply networks. Our previous study on gliomas showed that microvessel density was comparably less in VM-positive tumors than in VM-negative tumors. Thus, VM may act as a complement to ensure tumor blood supply, especially in regions with less microvessel density. Patients with VM-positive gliomas survived a shorter period of time than did patients with VM-negative gliomas. Although the detailed molecular mechanisms for VM are not fully understood, glioma stem cells might play a key role, since they are involved in tumor tissue remodeling and contribute to neovascularization via transdifferentiation. In the future, successful treatment of gliomas should involve targeting both VM and angiogenesis. In this review, we summarize the progress and challenges of VM in gliomas.

Figure 1.. Vasculogenic mimicry (VM) in human gliomas.

These representative images show gliomas dual stained for CD34 and periodic acid-schiff (PAS) using immunohistochemistry. A, endothelial cells are detected with anti-CD34 (dark brown), and vascular basement membrane is detected with PAS (purple magenta) in normal tubular blood vessels. B, microvascular proliferation of glioblastoma. C–F, typical VM channels (denoted by black arrows). The channels are located in a viable area of the tumor, far from necrosis. C and E, seven morphologic patterns of PAS-positive channels. D and F, VM channels containing red blood cells positive for PAS but negative for CD34: large cross section (D) and longitudinal section (F). Magnification: A, B, D, E, and F, ×400; C, ×100. (Cited from Yue et al.. The authors have got the permission to reprint this image.)

Figure 2.. Connection between the endothelial-lined vasculature and VM channels.

A, this longitudinal section dual stained for CD34 and periodic acid-schiff (PAS) shows a blood vessel with distinctive CD34⁺ (dark brown) and CD34⁻ but PAS⁺ portions (purple magenta) (magnification: ×400). (Cited from El Hallani et al.. The authors have got the permission to reprint this image.) B, absorbite particles, injected into the jugular vein, could be seen at human glioma stem cells, derived intracranial tumor vessels of various sizes. The inner lumens of these tumor vessels were irregular and discontinuous, and absorbite particles aggregated with red blood cells (HE staining, magnification: ×400). (Cited from Dong et al.. The authors have got the permission to reprint this image.)