title: M2-like tumor-associated macrophages drive vasculogenic mimicry through amplification of IL-6 expression in glioma cells.
abstract: Vasculogenic mimicry (VM) has offered a new horizon for understanding tumor angiogenesis, but the mechanisms of VM in glioma progression have not been studied explicitly until now. As a significant component of immune infiltration in tumor microenvironment, macrophages have been demonstrated to play an important role in tumor growth and angiogenesis. However, whether macrophages could play a potential key role in glioma VM is still poorly understood. Herein we reported that both VM and CD163+ cells were associated with WHO grade and reduced patient survival, and VM channel counting was correlated to the number of infiltrated CD163+ cells in glioma specimens. In vitro studies of glioma cell lines implicated that M2-like macrophages (M2) promoted glioma VM. We found that conditional medium derived from M2 amplified IL-6 expression in glioma cells. Furthermore, our data indicated that IL-6 could promote glioma VM, as blocking IL-6 with neutralizing antibodies abrogated M2-mediated VM enhancement. In addition, the potent PKC inhibitor bisindolylmaleimide I could prevent M2-induced IL-6 upregulation and further inhibited glioma VM facilitation. Taken together, our results suggested that M2-like macrophages drove glioma VM through amplifying IL-6 secretion in glioma cells via PKC pathway.
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, P.R. China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, P.R. China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, P.R. China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, P.R. China.
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, P.R. China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, P.R. China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, P.R. China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, P.R. China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, P.R. China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, P.R. China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, P.R. China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, P.R. China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, P.R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D005910:Glioma / Q000209:etiology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000276:immunology; D011379:Prognosis; D011493:Protein Kinase C / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D016207:Cytokines; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D011493:Protein Kinase C
keywords: IL-6; PKC; glioma; macrophages; vasculogenic mimicry