HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PlGF

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• 作者：Charlotte Rolny¹ ; ² ; ³ ; ¹⁰ ; Massimiliano Mazzone² ; ³ ; ¹⁰ ; Sò ; nia Tugues¹ ; Damya Laoui⁴ ; ⁵ ; Irja Johansson¹ ; Cathy Coulon² ; ³ ; Mario Leonardo Squadrito⁶ ; Inmaculada Segura² ; ³ ; Xiujuan Li¹ ; Ellen Knevels² ; ³ ; Sandra Costa² ; ³ ; Stefan Vinckier² ; ³ ; Tom Dresselaer⁷ ; Peter Å ; kerud⁸ ; Maria De Mol² ; ³ ; Henriikka Salomä ; ki¹ ; Mia Phillipson⁹ ; Sabine Wyns² ; ³ ; Erik Larsson¹ ; Ian Buysschaert² ; ³ ; Johan Botling¹ ; Uwe Himmelreich⁷ ; Jo A. Van Ginderachter⁴ ; ⁵ ; Michele De Palma⁶ ; Mieke Dewerchin² ; ³ ; Lena Claesson-Welsh¹ ; ¹¹ ; ^{lena.welsh@igp.uu.se} ; Peter Carmeliet² ; ³ ; ¹¹
• 刊名：Cancer Cell
• 出版年：2011
• 出版时间：18 January 2011
• 年：2011
• 卷：19
• 期：1
• 页码：31-44
• 全文大小：2446 K

文摘

Summary

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.