Open AccessHeat Shock Protein 47 Promotes Glioma Angiogenesis
Author(s) -
Wu Zhe Bao,
Cai Lin,
Lin Shao Jian,
Leng Zhi Gen,
Guo Yu Hang,
Yang Wen Lei,
Chu Yi Wei,
Yang ShaoHua,
Zhao Wei Guo
Publication year - 2016
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12256
Subject(s) - angiogenesis , glioma , gene knockdown , cancer research , heat shock protein , umbilical vein , gene silencing , biology , hsp70 , in vivo , chemistry , microbiology and biotechnology , in vitro , cell culture , biochemistry , gene , genetics
Abstract Heat shock protein 47 ( HSP 47) is a collagen‐binding protein, which has been recently found to express in glioma vessels. However, the expression profile of HSP 47 in glioma patients and the underlying mechanisms of HSP 47 on glioma angiogenesis are not fully explored. In the current study, we found that expression of HSP 47 in glioma vessels was correlated with the grades of gliomas. HSP 47 knockdown by siRNAs significantly decreased cell viability in vitro and tumor volume in vivo ; moreover, it reduced the microvessel density ( MVD ) by CD 31 immunohistochemistry in vivo . HSP 47 knockdown significantly inhibited tube formation, invasion and proliferation of human umbilical vein endothelial cells (HUVECs). Furthermore, conditional medium derived from HSP 47 knockdown cells significantly inhibited HUVECs tube formation and migration, while it increased chemosensitivity of HUVECs cells to A vastin. Silencing of HSP 47 decreased VEGF expression in glioma cells consistently, and reduced glioma vasculature. Furthermore, HSP 47 promoted glioma angiogenesis through HIF 1α‐ VEGFR 2 signaling. The present study demonstrates that HSP 47 promotes glioma angiogenesis and highlights the importance of HSP 47 as an attractive therapeutic target of GBM .