Autocrine VEGF – VEGFR 2 – Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth

The Rockefeller University Press $30.00 J. Exp. Med. Vol. 209 No. 3 507-520 www.jem.org/cgi/doi/10.1084/jem.20111424 507 GBM, the most prevalent primary malignant brain tumor in adults, is essentially universally fatal, despite maximal therapy. Robust neoangiogenesis and intratumoral heterogeneity are hallmark features of these brain malignancies, which contribute to their phenotypic plasticity and therapeutic resistance (Shen et al., 2008; Li et al., 2009a; Ricci-Vitiani et al., 2010; Wang et al., 2010; Soda et al., 2011). The latter includes drugs that target the angiogenic interplay between vascular endothelial growth factor (VEGF) and its receptors, VEGFRs. Recent observations suggest that anti-VEGF compounds (blocking antibodies and tyrosine kinase inhibitors), administered in combination with or before radiation, improve the responsiveness of solid tumors through radiosensitizing effects (Winkler et al., 2004; Citrin et al., 2006; Folkins et al., 2007; Vredenburgh et al., 2007; Desjardins et al., 2008; Ellis and Hicklin, 2008; Friedman et al., 2009; Gururangan et al., 2010; Lai et al., 2011). The concept of cancer stem-like cells (CSCs) in general, and their presence in glioblastoma CORRESPONDENCE J. Bartek: jb@cancer.dk OR J.N. Rich: richj@ccf.org