title: Redox status of high-mobility group box 1 performs a dual role in angiogenesis of colorectal carcinoma.
abstract: During inflammation, high-mobility group box 1 in reduced all-thiol form (at-HMGB1) takes charge of chemoattractant activity, whereas only disulfide-HMGB1 (ds-HMGB1) has cytokine activity. Also as pro-angiogenic inducer, the role of HMGB1 in different redox states has never been defined in tumour angiogenesis. To verify which redox states of HMGB1 induces angiogenesis in colorectal carcinoma. To measure the expression of VEGF-A and angiogenic properties of the endothelial cells (ECs), at-HMGB1 or ds-HMGB1 was added to cell medium, further with their special inhibitors (DPH1.1 mAb and 2G7 mAb) and antibodies of corresponding receptors (RAGE Ab and TLR4 Ab). Also, a co-culture system and conditioned medium from tumour cells were applied to mimic tumour microenvironment. HMGB1 triggered VEGF-A secretion mainly through its disulfide form interacting with TLR4, while co-operation of at-HMGB1 and RAGE mediated migratory capacity of ECs. Functional inhibition of HMGB1 and its receptors abrogated HMGB1-induced angiogenic properties of ECs co-cultured with tumour cells. HMGB1 orchestrates the key events of tumour angiogenesis, migration of ECs and their induction to secrete VEGF-A, by adopting distinct redox states.
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.|Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Lingyin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.|The First People's Hospital of Lianyungang, Jiangsu Provence, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ren
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Yingxuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fang
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Zhizheng
authors.initials: Z
authors.lastname: Ge
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D004220:Disulfides / Q000378:metabolism; D045325:HCT116 Cells; D024243:HMGB1 Protein / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066298:In Vitro Techniques; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010084:Oxidation-Reduction; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D004220:Disulfides; D024243:HMGB1 Protein; D042461:Vascular Endothelial Growth Factor A
keywords: VEGF-A; all-thiol form; disulfide form; high-mobility group box 1; tumour angiogenesis