title: Galunisertib inhibits glioma vasculogenic mimicry formation induced by astrocytes.
abstract: Gliomas are among the most lethal primary brain tumors found in humans. In high-grade gliomas, vasculogenic mimicry is often detected and has been correlated with prognosis, thus suggesting its potential as a therapeutic target. Vasculogenic mimicry mainly forms vascular-like channels independent of endothelial cells; however, little is known about the relationship between astrocytes and vasculogenic mimicry. In our study, we demonstrated that the presence of astrocytes promoted vasculogenic mimicry. With suspension microarray technology and in vitro tube formation assays, we identified that astrocytes relied on TGF-β1 to enhance vasculogenic mimicry. We also found that vasculogenic mimicry was inhibited by galunisertib, a promising TGF-β1 inhibitor currently being studied in an ongoing trial in glioma patients. The inhibition was partially attributed to a decrease in autophagy after galunisertib treatment. Moreover, we observed a decrease in VE-cadherin and smooth muscle actin-α expression, as well as down-regulation of Akt and Flk phosphorylation in galunisertib-treated glioma cells. By comparing tumor weight and volume in a xenograft model, we acquired promising results to support our theory. This study expands our understanding of the role of astrocytes in gliomas and demonstrates that galunisertib inhibits glioma vasculogenic mimicry induced by astrocytes.
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, China.|Brain Science Research Institute, Shandong University, 44 Wenhuaxi Road, Jinan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Brain Science Research Institute, Shandong University, 44 Wenhuaxi Road, Jinan, China.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, China.|Brain Science Research Institute, Shandong University, 44 Wenhuaxi Road, Jinan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Brain Science Research Institute, Shandong University, 44 Wenhuaxi Road, Jinan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Brain Science Research Institute, Shandong University, 44 Wenhuaxi Road, Jinan, China.
authors.forename: Aanjing
authors.initials: A
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences and Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Shandong University, 44 Wenhuaxi Road, Jinan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, China.|Brain Science Research Institute, Shandong University, 44 Wenhuaxi Road, Jinan, China.|Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009-Bergen, Norway.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, China.|Brain Science Research Institute, Shandong University, 44 Wenhuaxi Road, Jinan, China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051057:Proto-Oncogene Proteins c-akt; D011720:Pyrazoles; D011804:Quinolines; D053773:Transforming Growth Factor beta1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099152:Cadherin 5; C557799:LY-2157299