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 | Nan Zhao, Bao-cun Sun, Tao Sun, Yue-mei Ma, Xiu-lan Zhao, Zhi-yong Liu, Xue-yi Dong, Na Che, Jing Mo, Qiang Gu |
| Journal | Medical oncology (Northwood, London, England) (Med Oncol) Vol. 29 Issue 5 Pg. 3599-607 (Dec 2012) ISSN: 1559-131X [Electronic] United States |
| PMID | 22562824 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!