Secreted phosphoprotein 1 promotes angiogenesis of glioblastoma through upregulating PSMA expression via transcription factor HIF1α  

作　　者：Wenjing Tu Hui Zheng Liangdong Li Changshuai Zhou Mingtao Feng Lei Chen Deheng Li Xin Chen Bin Hao Huaping Sun Yiqun Cao Yang Gao 

机构地区：[1]Department of Neurosurgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China [2]Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China [3]Department of Nuclear Medicine,Shanghai Tenth People’s Hospital,Tongji University,Shanghai 200072,China [4]Department of Radiology,Huashan Hospital,Fudan University,Shanghai 200040,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第3期417-425,共9页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.82103429 and 82173177);the Foundation of Tenth People's Hospital(No.04.03.18.088);the Foundation of Shanghai Municipal Health Bureau(No.20204Y0264).

摘　　要：Glioblastoma multiforme(GBM)is a highly vascularized malignant brain tumor.Our previous study showed that prostate-specific membrane antigen(PSMA)promotes angiogenesis of GBM.However,the specific mechanism underlying GBM-induced PSMA upregulation remains unclear.In this study,we demonstrate that the GBM-secreted cytokine phosphoprotein 1(SPP1)can regulate the expression of PSMA in human umbilical vein endothelial cells(HUVECs).Our mechanistic study further reveals that SPP1 regulates the expression of PSMA through the transcription factor HIF1α.Moreover,SPP1 promotes HUVEC migration and tube formation.In addition,HIF1α knockdown reduces the expression of PSMA in HUVECs and blocks the ability of SPP1 to promote HUVEC migration and tube formation.We further confirm that SPP1 is abundantly expressed in GBM,is associated with poor prognosis,and has high clinical diagnostic value with considerable sensitivity and specificity.Collectively,our findings identify that the GBM-secreted cytokine SPP1 upregulates PSMA expression in endothelial cells via the transcription factor HIF1α,providing insight into the angiogenic process and promising candidates for targeted GBM therapy.

关 键 词：glioblastoma multiforme SPP1 PSMA ANGIOGENESIS HIF1Α 

分 类 号：R739.4[医药卫生—肿瘤]