title: HMGB1 promotes lymphangiogenesis of human lymphatic endothelial cells in vitro.
abstract: High-mobility group box 1 (HMGB1), a proinflammatory cytokine, plays an important role in inflammatory diseases, including severe sepsis and arthritis. This recent discovery of the extracellular role of HMGB1 as a multifunctional cytokine involved in tumorigenesis, tumor angiogenesis as well as metastasis has opened up a new field of research to study the role of HMGB1 in tumors. However, its molecular mechanism in lymphangiogenesis remains poorly understood. In this study, human lymphatic endothelial cells (LECs) were treated with human recombinant HMGB1 (rHMGB1) and recombinant VEGF-C (rVEGF-C). Changes in cell proliferation, migration, and the capillary-like tube formation were assessed by MTT assay, transwell chamber assay, and a Matrigel model, respectively. Human rHMGB1 induced LEC proliferation, migration, and tube formation in a dose- and time-dependent manner with the maximal effect at a concentration of 2 μg/ml. As a specific lymphangiogenes factor, the role of rVEGF-C in promoting lymphangiogenesis was significant. These data indicate, for the first time, that HMGB1 might contribute to tumor lymphangiogenesis and lymphatic metastasis, and it might ultimately represent a therapeutic target in tumor patients.
authors.affiliation: Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. yuanyuanqingsong@gmail.com
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qiu
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Fu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; D011994:Recombinant Proteins; D042582:Vascular Endothelial Growth Factor C