title: Hypoxia-induced vasculogenic mimicry formation via VE-cadherin regulation by Bcl-2.
abstract: Vasculogenic mimicry (VM) refers to the unique ability of highly aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Hypoxia plays a pivotal role in the formation of VM. Hypoxia-induced Bcl-2 overexpression is observed in many types of tumors including melanoma, in which it is associated with tumorigenicity and angiogenesis. VE-cadherin, the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation, is also overexpressed in melanoma. Despite these connections, whether hypoxia induces VM formation via VE-cadherin regulation by Bcl-2 is not confirmed. We used human melanoma cells to upregulate or knockdown the expression of Bcl-2 to investigate the possible molecular mechanism of VM formation under hypoxia. Bcl-2 overexpression increased VE-cadherin expression and VM formation under normoxia, whereas Bcl-2 siRNA significantly decreased VE-cadherin expression and VM formation under hypoxia. We then demonstrated that Bcl-2 regulated VE-cadherin transcription activity by Western blot, three-dimensional cultures, reporter gene assay, and clinical analysis. Therefore, Bcl-2-dependent VE-cadherin overexpression may be an important mechanism by which hypoxia induces VM.
authors.affiliation: Department of Pathology, Tianjin Medical University, Heping District Qixiangtai Road No. 22, Tianjin, 300070, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.forename: Bao-cun
authors.initials: BC
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Yue-mei
authors.initials: YM
authors.lastname: Ma
authors.forename: Xiu-lan
authors.initials: XL
authors.lastname: Zhao
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Liu
authors.forename: Xue-yi
authors.initials: XY
authors.lastname: Dong
authors.forename: Na
authors.initials: N
authors.lastname: Che
authors.forename: Jing
authors.initials: J
authors.lastname: Mo
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D001808:Blood Vessels; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D018716:Molecular Mimicry / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D019253:Proto-Oncogene Proteins c-bcl-2; D000099152:Cadherin 5