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

Rolny, C. et al. Cancer Cell. 2011; 19: 31-44.

Speaker:  Ming-Hsien Tsai (蔡明憲)                     Time: 15:00~16:00 , Sep. 21, 2011

Commentator: Bei-Chang Yang (楊倍昌博士)    Place: Room 601

Abstract:

Tumor-associated macrophages (TAMs) divided into two phenotypes, tumor inhibiting M1-like phenotype and tumor promoting M2-like phenotype, M2 proliferation in the tumor result in patient's poor prognosis. Because of M2’s immune suppression and angiogenesis function. Because of tumor have abnormal angiogenesis function, so the cancer patients can be found abnormal blood vessels in the tumor, which causes blood vessel function poorly, oxygenation and chemotherapy are impaired, may result tumor hypoxia, increased risk of cancer metastasis. So the “normalization” of vascular function strategies are gaining attention. In this study, the researchers found that a multi-domain protein, histidine-rich glycoprotein (HRG) can inhibit tumor growth and metastasis, it also can improve the effectiveness of chemotherapy. Further study, by skewing the TAM polarization form M2-like phenotype to M1-like phenotype, HRG promote antitumor immune response and normalization blood vessels, result the risk of metastasis decreased, and enhancing the effectiveness of chemotherapy, in which most likely through downregulation placental growth factor (PlGF). This study established TAM polarization to have an important role in tumor vessel abnormalization, and its regulation by HRG and PlGF, this finding offer therapeutic opportunities for anticancer or antiangiogenic treatment.

References:

1.      Yuhui Huang, Matija Snuderl, and Rakesh K. Jain. Polarization of tumor-associated macrophages: A novel strategy for vascular normalization and antitumor immunity. Cancer Cell 19, 1-2 (2011).

2.      Fischer, C., Mazzone, M., Jonckx, B., and Carmeliet, P. (2008). FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? Nat. Rev. Cancer 8, 942–956.