Open AccessRedox status of high‐mobility group box 1 performs a dual role in angiogenesis of colorectal carcinoma
Author(s) -
Zhu Lingyin,
Ren Lin,
Chen Yingxuan,
Fang Jingyuan,
Ge Zhizheng,
Li Xiaobo
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12577
Subject(s) - hmgb1 , angiogenesis , rage (emotion) , cancer research , cell migration , receptor , chemistry , microbiology and biotechnology , biology , cell , biochemistry , neuroscience
During inflammation, high‐mobility group box 1 in reduced all‐thiol form (at‐ HMGB 1) takes charge of chemoattractant activity, whereas only disulfide‐ HMGB 1 (ds‐ HMGB 1) has cytokine activity. Also as pro‐angiogenic inducer, the role of HMGB 1 in different redox states has never been defined in tumour angiogenesis. To verify which redox states of HMGB 1 induces angiogenesis in colorectal carcinoma. To measure the expression of VEGF ‐A and angiogenic properties of the endothelial cells ( EC s), at‐ HMGB 1 or ds‐ HMGB 1 was added to cell medium, further with their special inhibitors ( DPH 1.1 mAb and 2G7 mAb) and antibodies of corresponding receptors ( RAGE Ab and TLR 4 Ab). Also, a co‐culture system and conditioned medium from tumour cells were applied to mimic tumour microenvironment. HMGB 1 triggered VEGF ‐A secretion mainly through its disulfide form interacting with TLR 4, while co‐operation of at‐ HMGB 1 and RAGE mediated migratory capacity of EC s. Functional inhibition of HMGB 1 and its receptors abrogated HMGB 1‐induced angiogenic properties of EC s co‐cultured with tumour cells. HMGB 1 orchestrates the key events of tumour angiogenesis, migration of EC s and their induction to secrete VEGF ‐A, by adopting distinct redox states.