Glioblastoma (GBM) tumors secrete high level of angiogenic factors and feature vascular abnormality. Targeted therapy, such as Bevacizumab, which neutralizes VEGF and normalizes tumor vasculature, has been approved to treat recurrent GBM. However, it only marginally increases patients' overall survival with inevitable resistance. It suggests that therapy targeting complementary angiogenic pathway in GBM could suppress Bevacizumab resistance and extend patients' survival.

Angiogenin (ANG) is involved in tumor angiogenesis where it regulates ribosomal RNA transcription and functions downstream of VEGF and other related angiogenic factors. Like VEGF, ANG is also up-regulated in GBM patients. Inhibition of ANG by neutralizing monoclonal antibody delays U87 human GBM xenografts on nude mice. My preliminary data have shown that ANG is essential for GBM cell line s.c. vessel formation and tumor proliferation. In Rcas/tva orthotropic GBM model, Ang1 knockout mice show lower penetration and better survivals. ANG knockdown increases apoptosis during GBM cell line colony formation in agarose. Notably, ANG's role in tumor proliferation might extend beyond GBM, since oncogenic KRas transformed Ang1 knockout MEFs also fail to grow in agarose. Lastly, I have shown that PlexinB2, ANG cellular receptor, can mediate ANG cellular uptake and also modulate GBM apoptosis in agarose. In conclusion, inhibition of ANG inhibits GBM progression both in vitro and in vivo and thus represents a new molecular target for GBM treatment.

Citation Format: Hailing Yang, Guo-fu Hu. Angiogenin and PlexinB2 promote glioblastoma progression by stimulating tumor angiogenesis, cancer cell survival and invasion. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3934. doi:10.1158/1538-7445.AM2014-3934