HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PIGF
HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PIGF
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DOI：
10.1016/j.ccr.2010.11.009
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发表时间：
2011-01-18
期刊：
影响因子：
50.3
通讯作者：
Carmeliet, Peter
中科院分区：
文献类型：
--
作者：
Rolny, Charlotte;Mazzone, Massimiliano;Carmeliet, Peter
肿瘤相关巨噬细胞（tam）极化为促血管生成/免疫抑制（m2样）表型和异常、低灌注血管是恶性肿瘤的标志，但它们的分子基础和相互关系仍然是谜。我们报道宿主产生的富组氨酸糖蛋白（HRG）抑制肿瘤生长和转移，同时改善化疗。通过将TAM极化从M2-向肿瘤抑制m1样表型倾斜，HRG促进抗肿瘤免疫反应和血管正常化，已知其作用可减少肿瘤生长和转移，并增强化疗。HAG导致TAM极化偏斜主要依赖于胎盘生长因子（PIGF）的下调。除了揭示TAM极化在肿瘤血管异常中的重要作用，以及HRG/PIGF对其的调节外，这些发现还为抗癌和抗血管生成治疗提供了治疗机会。
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.