cRGD inhibits vasculogenic mimicry formation by down-regulating uPA expression and reducing EMT in ovarian cancer
Metrics: PDF 758 views | HTML 1021 views | ?
Jiao Tang1,2,*, Jianguo Wang2,*, Lin Fan3, Xiaoxuan Li1, Na Liu1, Wanxian Luo2, Jihui Wang2, Yifeng Wang1, Ying Wang2
1Department of Obstetrics & Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
2Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
3Department of Reproductive Medicine Center, The Women and Children Hospital of Guangdong, Guangzhou Medical University, Guangzhou 511442, China
*These authors have contributed equally to this work
Ying Wang, e-mail: email@example.com
Yifeng Wang, e-mail: firstname.lastname@example.org
Keywords: vasculogenic mimicry, uPA, cRGD, epithelial-mesenchymal transition, ovarian cancer
Received: November 05, 2015 Accepted: February 29, 2016 Published: March 15, 2016
Vasculogenic minicry (VM), an alternative blood supply modality except to endothelial cells-mediated vascular network, is a potential therapeutic target for ovarian cancer due to VM correlated with poor prognosis in ovarian cancer patients. Accelerated extracellular matrix (ECM) degradation is prerequisite for VM formation induced by epithelial-mesenchymal transition (EMT). Previous reports demonstrate uPA has ability to degrade ECM thereby promoting tumor angiogenesis. Also, exogenous cRGD sequence enables to modulate uPA expression, attenuate EMT and suppress endothelial-lined channels. Till now, the correlation of uPA and VM formation and the effect of exogenous cRGD on VM formation remain unknown. Herein, we validate uPA expression is positively correlated with VM formation in ovarian cancer tissues (90 cases) and ovarian cancer cells (SKOV-3, OVCAR-3 and A2780 cells). In particular, silencing uPA experiments show that down-regulated uPA causes notable decrease for the complete channels formed by SKOV-3 and OVCAR-3 cells. Mechanism study discloses uPA promotes VM formation by regulating AKT/mTOR/MMP-2/Laminin5γ2 signal pathway. The result demonstrates uPA may serve as therapeutic target of VM for ovarian cancer. Also, it is found exogenous cRGD enables to inhibit VM formation in ovarian cancer via not only down-regulating uPA expression but also reducing EMT. Exogenous cRGD may be a promising angiogenic inhibitor for ovarian cancer therapy due to its inhibiting effect on VM formation as well as endothelial cells-mediated vascular network.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.