ABSTRACT
CSCs regulate angiogenesis by mutually modulately their microenvironment through direct cell-cell communication (Frank et al. 2010) or paracrine factors secretion. First, CSCs positive for Nestin+ [a type VI intermediate filament (IF) protein] and CD133+ (that mark neural stem and progenitor cells) reside within a specific perivascular niches in various brain tumors (oligodendrogliomas, gliobalstomas, medulloblastomas and ependymomas), where they interact tightly with endothelial cells. It is postulated that through this interaction the endothelial cells maintain Nestin+/CD133+ CSCs in a self-renewing and undifferentiated state (Calabrese et al. 2007). Second, paracrine factors released from CSCs could strength the process of angiogenesis (Bao et al. 2006). For instance, the CD133+ glioma-initiating cells in human glioma cell-derived xenografts secreted high levels of VEGF, which specifically promoted tumor angiogenesis and therefore tumor xenograft growth (Bao et al. 2006). Inhibition of either ERBB2 or VEGF signaling significantly reduced the CD133+ CSCs abundance and suppressed the growth of tumor xenograft growth (Bao et al. 2006; Calabrese et al. 2007). Glioma CSCs also preferentially expressed HIF2a and many HIF-regulated genes, which was directly linked to stem cell-like tumor cells (Bleau et al. 2009) and is critical for self-renewal of hematopoietic stem cells (Miyamoto et al. 2007; Li et al. 2009). Third, cancer stem cells such as glioma stem/progenitor cells (GSPCs) could participate in angiogenesis by trans-differentiating themselves into vascular endothelial cells (VEC). It has been suggested that GSPCs transcribe or copy functions and also can express VEC characteristic molecular markers (Zhao et al. 2010).
