Angiogenesis causes and vasculogenic mimicry formation in the context of cancer stem cells

Abstract

Tumor occurrence, development, invasion, and metastasis are regulated by multiple mechanisms. Among these, angiogenesis promotes tumor progression mainly by supplying tumor tissue and providing channels for tumor metastasis. Cancer stem cells (CSCs) are another important factor affecting tumor progression by involving in tumor initiation and development, while remaining insensitive to conventional antitumor treatments. Among treatment strategies for them, owing to the existence of alternative angiogenic pathways or the risk of damaging normal stem cells, the clinical effect is not ideal. Angiogenesis and CSCs may influence each other in this process. Tumor angiogenesis can support CSC self-renewal by providing a suitable microenvironment, whereas CSCs can regulate tumor neovascularization and mediate drug resistance to anti-angiogenic therapy. This review summarized the role of vascular niche formed by angiogenesis in CSC self-renewal and stemness maintenance, and the function of CSCs in endothelial progenitor cell differentiation and pro-angiogenic factor upregulation. We also elucidated the malignant loop between CSCs and angiogenesis promoting tumor progression. Additionally, we summarized and proposed therapeutic targets, including blocking tumor-derived endothelial differentiation, inhibiting pro-angiogenic factor upregulation, and directly targeting endothelial-like cells comprising CSCs. And we analyzed the feasibility of these strategies to identify more effective methods to improve tumor treatment.

Keywords: Angiogenesis; Cancer stem cell; Tumor microenvironment; Tumor therapy; Vasculogenic mimicry.