Resisting arrest: a switch from angiogenesis to vasculogenesis in recurrent malignant gliomas

Abstract

The cellular and molecular events that initiate and promote malignant glioma development are not completely understood. The treatment modalities designed to promote its demise are all ultimately ineffective, leading to disease progression. In this issue of the JCI, Kioi et al. demonstrate that vasculogenesis and angiogenesis potentially play distinct roles in the etiology of primary and recurrent malignant gliomas, suggesting that patient therapy should perhaps be tailored specifically against the predominant vasculature pathway at a given specific stage of gliomagenesis.

Figure 1. Angiogenesis and vasculogenesis in primary occurrence versus recurrence of malignant glioma.

GBM is hypothesized to result from malignant transformation of astrocytes, astrocytic precursors, or neuronal stem cells, and these cells are capable of inducing their own blood supply (25). At initial presentation, it is hypothesized that angiogenesis is largely responsible for neovascularization of GBM. Release of factors such as VEGF, EGF, and FGF from tumor cells stimulates local sprouting of vessels, while recruitment of BMDCs likely plays a minor role. During tumor recurrence after radiation therapy, local sprouting of vessels is largely abrogated, allowing the recruitment of BMDCs to predominate as the main source of neovasculogenesis. In the current issue of the JCI, Kioi et al. (1) identify a potential vasculogenesis pathway whereby hypoxia within the tumor after radiation therapy stimulates HIF-1 release and subsequently elevates SDF-1. Activation of the CXCR4 receptor by SDF-1 promotes mobilization of bone marrow cells, which are then recruited to form new vessels.