American Association for Cancer Research
00085472can141240-sup-130530_1_supp_2626319_nspysd.pptx (22.26 MB)

Supplementary Figure 2 from RAGE Expression in Tumor-Associated Macrophages Promotes Angiogenesis in Glioma

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posted on 2023-03-30, 22:41 authored by Xuebo Chen, Leying Zhang, Ian Y. Zhang, Junling Liang, Huaqing Wang, Mao Ouyang, Shihua Wu, Anna Carolina Carvalho da Fonseca, Lihong Weng, Yasuhiko Yamamoto, Hiroshi Yamamoto, Rama Natarajan, Behnam Badie

Supplementary Fig. 2: RAGE ablation in GL261 gliomas results in the formation of dilated, leaky vessels.



Interaction of RAGE (the receptor for advanced glycation endproducts) with its ligands can promote tumor progression, invasion, and angiogenesis. Although blocking RAGE signaling has been proposed as a potential anticancer strategy, functional contributions of RAGE expression in the tumor microenvironment (TME) have not been investigated in detail. Here, we evaluated the effect of genetic depletion of RAGE in TME on the growth of gliomas. In both invasive and noninvasive glioma models, animal survival was prolonged in RAGE knockout (Ager−/−) mice. However, the improvement in survival in Ager−/− mice was not due to changes in tumor growth rate but rather to a reduction in tumor-associated inflammation. Furthermore, RAGE ablation in the TME abrogated angiogenesis by downregulating the expression of proangiogenic factors, which prevented normal vessel formation, thereby generating a leaky vasculature. These alterations were most prominent in noninvasive gliomas, in which the expression of VEGF and proinflammatory cytokines were also lower in tumor-associated macrophages (TAM) in Ager−/− mice. Interestingly, reconstitution of Ager−/− TAM with wild-type microglia or macrophages normalized tumor vascularity. Our results establish that RAGE signaling in glioma-associated microglia and TAM drives angiogenesis, underscoring the complex role of RAGE and its ligands in gliomagenesis. Cancer Res; 74(24); 7285–97. ©2014 AACR.