IDH1 mutation promotes angiogenesis via upregulation of hypoxia inducible factor 1 alpha in glial tumors.

Glial tumors are the most common malignant brain tumors, and IDH1 serves as an important diagnostic and prognostic molecular marker in gliomas. The mutation status of IDH1 influences prognosis, patient survival, and treatment response in glial tumors. However, the effects of the IDH1 mutation on the angiogenic potential of glial tumors have yet to be thoroughly elucidated. Our aim was to investigate the impact of the IDH1 mutation on the angiogenic potential of glial tumors by overexpressing both mutant and wild-type IDH1 genes in these tumors. Furthermore, we examined how the signaling pathways affecting the angiogenic behavior of glial tumors differ based on IDH1 mutation status by evaluating the mRNA expressions of VEGF, EGF, PDGF, and FGF signaling pathways in the U87MG cell line as well as in patient-derived tumor samples. The IDH1 mutation induced proliferation and tube-formation potential in U87MG cells while suppressing these activities in HUVEC cells. Considering angiogenesis-associated signaling pathways, we found that mutant IDH1 expression indirectly upregulates angiogenesis-associated pathways via HIF1A. The genes VEGFC, ERBB3, PDGFB, and PDGFC may serve as potential markers for the prognosis of glial tumors and for anti-angiogenic therapy.