HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PIGF (Cancer Cell, 2011, 19:31-44)

報告日期: 2011/04/01
報告時間: 16:00/16:50
報告學生: 林長霓
講評老師: 凌 斌
附件下載:

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0401-2.pdf

HGR Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PlGF
 
Charlotte Rolny, Massimiliano Mazzone, Sonia Tugues, et al. Cancer Cell 19, 31-44, 2011
 
Speaker: Lin, Chang-Ni
Commentator: Ling, Pin, Ph.D.
Date: 2011/4/1
Location: Room 602
 
Abstract
Background:
 The tumor microenvironment is now well accepted to research tumorigenesis. Tumor-associated macrophages (TAMs) are a major component of leukocytic infiltrate of tumors and enhance tumor progression to malignancy by tumor immune responses and angiogenesis. TAMs infiltration is associated with an unfavorable prognosis, which can be re-educated by immunoregulation1.
Histidine-rich glycoprotein (HRG), a host-produced glycoprotein that has been found antitumor activity through modulates angiogenesis, was first isolated in 19722. Although HRG inhibits tumor growth, its precise mechanisms still incompletely know, like metastasis and immune regulation. This paper link HRG and TAMs cause tumor vessel normalization via PlGF (placental growth factor) downregulation.
Objectives:
 To identify mechanisms mediating the antitumor effects of HRG, especially correlation of immune modulatory function.
Results:
 In this study, HRG has been characteristic to skew TAMs polarization away from the M2- to a tumor-inhibiting M1-like phenotype through M2 signature genes downregulation. HRG is a host-produced glycoprotein deposited in the tumor stroma increased the host-antitumor immune response and promote tumor vessel normalization through PlGF downregulation. The findings provide HRG promote vessel normalization strategies in silencing metastasis and reeducation of TAMs polarization is a promising anticancer treatment strategy.
Conclusions:
 HRG play a role in vessel normalization through macrophage polarization by PlGF downregulation; the results provide an anticancer drug target by enhancing immunity and vessel normalization.
 
References
1.     Movahedi K, Laoui D, Gysemans C, et al. Different tumor microenvienment contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 2010; 70: 5728-5739.
2.     Jones AL, Hulett MD, and Parish CR. Histidine-rich glycoprotein: A novel adaptor protein in plasma that modulates the immune, vascular and coagulation systems. Immuno Cell Biol. 2005; 83: 106-118.