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. © 2011 Elsevier Inc.

HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF

Mazzone M.;
2011-01-01

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. © 2011 Elsevier Inc.
2011
Animals
Antibodies
CD8-Positive T-Lymphocytes
Cell Line
Tumor
Cell Proliferation
Chemotactic Factors
Clodronic Acid
Culture Media
Conditioned
Cytokines
Dendritic Cells
Down-Regulation
Endothelial Cells
Gene Expression
Humans
Hypoxia
Lung Neoplasms
Macrophages
Macrophages
Peritoneal
Mice
Mice
Inbred BALB C
Mice
Inbred C57BL
Mice
Knockout
Microvessels
Neoplasm Metastasis
Neoplasms
Neovascularization
Pathologic
Placenta Growth Factor
Pregnancy Proteins
Proteins
Regional Blood Flow
Transfection
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/83030
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