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HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PIGF
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology. (Forskargrupp Rolny)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Cancer and Vascular Biology. (Forskargrupp Claesson-Welsh)
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2011 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 19, no 1, 31-44 p.Article in journal (Refereed) Published
Abstract [en]

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 HAG relies substantially on downregulation of placental growth factor (PIGF). Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PIGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment.

Place, publisher, year, edition, pages
2011. Vol. 19, no 1, 31-44 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-149047DOI: 10.1016/j.ccr.2010.11.009ISI: 000287290300008PubMedID: 21215706OAI: oai:DiVA.org:uu-149047DiVA: diva2:403837
Note

De två första författarna delar förstaförfattarskapet.

De två sista författarna delar sistaförfattarskapet.

Available from: 2011-03-15 Created: 2011-03-15 Last updated: 2017-12-11Bibliographically approved

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Li, XiujuanÅkerud, PeterPhillipson, MiaLarsson, ErikBotling, JohanClaesson-Welsh, Lena

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