title: Bio-HMGB1 from breast cancer contributes to M-MDSC differentiation from bone marrow progenitor cells and facilitates conversion of monocytes into MDSC-like cells.
abstract: Myeloid-derived suppressor cells (MDSC) constitute the major cell population that regulates immune responses. They are known to accumulate in tumors, chronic inflammatory and autoimmune diseases. Previous data indicate that high mobility group box 1(HMGB1) facilitates MDSC differentiation from bone marrow, suppresses NK cells, CD4+and CD8+T cells and is involved in cancer development. However, it remains unclear what potential mechanisms of HMGB1 facilitate MDSC differentiation. In the present work, we clearly demonstrate that HMGB1 secreted by cancer cells is N-glycosylated at Asn37, which facilitates monocytic (M)-MDSC differentiation from bone marrow via the p38/NFκB/Erk1/2 pathway and also contributes to conversion of monocytes into MDSC-like cells; HMGB1 blockade by a monoclonal antibody against the HMGB1 B box obviously reduced the accumulation of M-MDSC in tumor-bearing mice, delaying tumor growth and development; additionally, MDSC expansion and HMGB1 up-regulation were also found in breast cancer patients. All these data indicate that HMGB1 might be a potential tumor immunotherapy target.
authors.affiliation: The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China.|Department of Immunology, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Immunology, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ni
authors.affiliation: Department of Immunology, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: She
authors.affiliation: The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China.
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Immunology, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
authors.forename: Seidu A
authors.initials: SA
authors.lastname: Richard
authors.affiliation: The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Xu
authors.affiliation: The Central Laboratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, China. szl30@sina.com.|Department of Immunology, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China. szl30@sina.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009000:Monocytes / Q000473:pathology*; D000072737:Myeloid-Derived Suppressor Cells / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology; D015854:Up-Regulation
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human
keywords: Breast cancer; HMGB1; MDSC; N-glycosylation