Vasorin Exocytosed from Glioma Cells Facilitates Angiogenesis via VEGFR2/AKT Signaling Pathway

作者：Ying Zhong, Hui Kang, Ziqing Ma, Jiayu Li, Zixi Qin, Zixuan Zhang, Peiwen Li, Ying Zhong, Lihui Wang · 发表于：Molecular Cancer Research · 年份：2024 · DOI：10.1158/1541-7786.mcr-23-0469 · 被引用次数：6 · 研究领域：Angiogenesis and VEGF in Cancer、Caveolin-1 and cellular processes、Proteoglycans and glycosaminoglycans research

Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial cells (hEC) co-cultured with VASN-overexpressing glioma cells exhibited accelerated migration ability and increased expression of VASN originated from glioma cells. VASN was found in exosomes secreted by glioma cells and could be taken up by hECs. hECs showed more edge filopodia and significantly upregulated expression of endothelial tip cell marker gene and protein levels after co-culture with VASN-overexpressing glioma cells. In clinical glioma tissue and orthotopic transplantation glioma tissue, the vascular density and the number of vascular endothelial cells with a tip cell phenotype in VASN-overexpressed tissues were significantly higher than in tissues with low expression. At the molecular level, VASN interacted with VEGFR2 and caused internalization and autophosphorylation of VEGFR2 protein, and then activated the AKT signaling pathway. Our study collectively reveals the function and mechanism of VASN in facilitating angiogenesis in glioma, providing a new therapeutic target for glioma. IMPLICATIONS: These findings demonstrate that VASN exocytosed from glioma cell...