HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF
- PMID: 21215706
- DOI: 10.1016/j.ccr.2010.11.009
HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF
Abstract
Polarization of tumor-associated macrophages (TAMs) to a proangiogenic/immune-suppressive (M2-like) phenotype and abnormal, hypoperfused vessels are hallmarks of malignancy, but their molecular basis and interrelationship remains enigmatic. We report that the host-produced histidine-rich glycoprotein (HRG) inhibits tumor growth and metastasis, while improving chemotherapy. By skewing TAM polarization away from the M2- to a tumor-inhibiting M1-like phenotype, HRG promotes antitumor immune responses and vessel normalization, effects known to decrease tumor growth and metastasis and to enhance chemotherapy. Skewing of TAM polarization by HRG relies substantially on downregulation of placental growth factor (PlGF). Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PlGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment.
Copyright © 2011 Elsevier Inc. All rights reserved.
Comment in
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Polarization of tumor-associated macrophages: a novel strategy for vascular normalization and antitumor immunity.Cancer Cell. 2011 Jan 18;19(1):1-2. doi: 10.1016/j.ccr.2011.01.005. Cancer Cell. 2011. PMID: 21251607 Free PMC article.
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Cancer: Re-educating tumour-associated macrophages.Nat Rev Drug Discov. 2011 Mar;10(3):177. doi: 10.1038/nrd3399. Nat Rev Drug Discov. 2011. PMID: 21358735 No abstract available.
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