SPP1 and neoplasm: In gliomas, OPN directly stimulates angiogenesis via the αvβ3/PI3K/AKT/eNOS/NO signaling pathway and may play an important role in tumorigenesis by enhancing angiogenesis in gliomas [39,40] In tumor angiogenesis, malignancy, invasion, and metastasis; hypoxia is a unique parameter.