Tan Qijia, Li Feng, Wang Jun, Zou Yuxi, Tang Yanping, Cai Yingqian, Jiang Xiaodan
Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Department of Neurosurgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
J Cancer. 2025 Jan 1;16(3):750-764. doi: 10.7150/jca.101050. eCollection 2025.
Glioblastoma (GBM) is a highly invasive and malignant primary intracranial tumor originating from glial cells, and it is associated with an extremely poor clinical prognosis. The hypoxic conditions within GBM promote various tumor cell processes such as angiogenesis, proliferation, migration, invasion, and drug resistance. A key aspect of tumor adaptation to the hypoxic environment and the promotion of malignant behaviors is the regulation of HIF-1α signaling pathways. However, the specific pathogenic mechanisms involving HIF-1α in GBM have not been thoroughly investigated. This study reveals significant overexpression of both HIF-1α and CD47 in GBM. Patients with high HIF-1α levels and CD47 expression had significantly reduced overall survival and disease-free survival times. Furthermore, a positive correlation was observed between the expression levels of HIF-1α and CD47 in GBM. Lentivirus-mediated knockdown of HIF-1α protein and plasmid-based overexpression of CD47 protein simultaneously enhanced cell proliferation, clonogenic potential and cell migration abilities in GBM, and HIF-1α was found to regulate key pathways, including the P-PI3K/P-AKT, SOX2/OCT4 and MMP2/MMP9 pathways, in GBM.
胶质母细胞瘤（GBM）是一种起源于神经胶质细胞的具有高度侵袭性和恶性的原发性颅内肿瘤，其临床预后极差。GBM内的缺氧状态会促进多种肿瘤细胞进程，如血管生成、增殖、迁移、侵袭和耐药性。肿瘤适应缺氧环境并促进恶性行为的一个关键方面是对缺氧诱导因子-1α（HIF-1α）信号通路的调控。然而，GBM中涉及HIF-1α的具体致病机制尚未得到充分研究。本研究揭示了GBM中HIF-1α和CD47均显著过表达。HIF-1α水平高且有CD47表达的患者总生存期和无病生存期显著缩短。此外，GBM中HIF-1α和CD47的表达水平之间存在正相关。慢病毒介导的HIF-1α蛋白敲低和基于质粒的CD47蛋白过表达同时增强了GBM中的细胞增殖、克隆形成潜力和细胞迁移能力，并且发现HIF-1α在GBM中调节关键通路，包括P-PI3K/P-AKT、SOX2/OCT4和MMP2/MMP9通路。
