Class A1 scavenger receptor modulates glioma progression by regulating M2-like tumor-associated macrophage polarization
Metrics: PDF 3133 views | HTML 2426 views | ?
Hanwen Zhang1, Wenbin Zhang2, Xuan Sun1, Ruoyu Dang1, Rongmei Zhou1, Hui Bai1, Jingjing Ben1, Xudong Zhu1, Yan Zhang1, Qing Yang1, Yong Xu1, Qi Chen1
1Department of Pathophysiology, Nanjing Medical University, Nanjing, P.R. China
2Department of Neurosurgery, Brain Hospital affiliated to Nanjing Medical University, Nanjing, P.R. China
Qi Chen, email: email@example.com
Keywords: glioma, tumor-associated macrophage, class A1 scavenger receptor, macrophage polarization, heat shock protein 70
Received: December 02, 2015 Accepted: June 12, 2016 Published: June 29, 2016
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.