title: Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization.
abstract: Macrophages enhance glioma development and progression by shaping the tumor microenvironment. Class A1 scavenger receptor (SR-A1), a pattern recognition receptor primarily expressed in macrophages, is up-regulated in many human solid tumors. We found that SR-A1 expression in 136 human gliomas was positively correlated with tumor grade (P<0.01), but not prognosis or tumor recurrence. SR-A1-expressing macrophages originated primarily from circulating monocytes attracted to tumor tissue, and were almost twice as numerous as resident microglia in glioma tissues (P<0.001). The effects of SR-A1 on glioma proliferation and invasion were assessed in vivo using an SR-A1-deficient murine orthotopic glioma model. SR-A1 deletion promoted M2-like tumor-associated macrophage (TAM) polarization in mice by activating STAT3 and STAT6, which resulted in robust orthotopic glioma proliferation and angiogenesis. Finally, we found that HSP70 might be an endogenous ligand that activates SR-A1-dependent anti-tumorigenic pathways in gliomas, although its expression does not appear informative for diagnostic purposes. Our findings demonstrate a relationship between TAMs, SR-A1 expression and glioma growth and provide new insights into the pathogenic role of TAMs in glioma.
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Brain Hospital affiliated to Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Dang
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Rongmei
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Bai
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ben
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; C503566:SCAF1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D000068103:Serine-Arginine Splicing Factors
keywords: class A1 scavenger receptor; glioma; heat shock protein 70; macrophage polarization; tumor-associated macrophage