Author/Authors :
Vinzent Rolny، نويسنده , , Charlotte and Mazzone، نويسنده , , Massimiliano and Tugues، نويسنده , , Sٍnia and Laoui، نويسنده , , Damya and Johansson، نويسنده , , Irja and Coulon، نويسنده , , Cathy and Squadrito، نويسنده , , Mario Leonardo and Segura، نويسنده , , Inmaculada and Li، نويسنده , , Xiujuan and Knevels، نويسنده , , Ellen and Costa، نويسنده , , Sandra and Vinckier، نويسنده , , Stefan and Dresselaer، نويسنده , , Tom and إkerud، نويسنده , , Peter and De Mol، نويسنده , , Maria and Salomنki، نويسنده , , Henriikka and Phillipson، نويسنده , , Mia and Wyns، نويسنده , , Sabine and Larsson، نويسنده , , Erik and Buysschaert، نويسنده , , Ian and Botling، نويسنده , , Johan and Himmelreich، نويسنده , , Uwe and Van Ginderachter، نويسنده , , Jo A. and De Palma، نويسنده , , Michele and Dewerchin، نويسنده , , Mieke and Claesson-Welsh، نويسنده , , Lena and Carmeliet، نويسنده , , Peter، نويسنده ,
Abstract :
Summary
zation 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.
