The growth of ovarian carcinoma is dependent upon their vascularistion, but the interaction of ovarian cancer cells with the endothelium and their invasion through an endothelial environment remain poorly understood at the molecular level. To investigate adhesive events underlying this process with focusing on the role of αv integrins and MT1MMP‐MMP2 proteinases, we used in vitro models of cocultures of human ovarian adenocarcinoma cell lines (IGROV1 and SKOV3) with human umbilical vein endothelial cells (HUVECs). Immunostaining of HUVECs revealed the network organisation of fibrillar fibronectin (Fn) and pericellular vitronectin (Vn). During coculture, IGROV1 and SKOV3 cells gain access to subendothelial basement membrane of HUVECs and dislocated endothelial Fn without affecting endothelial Vn. Transmigration assays revealed that tumour cells invade Vn and, with an higher efficiency, Fn. Our data also highlighted that ovarian carcinoma cells migrated through the Fn‐rich HUVEC‐ECM. The expression of MMP2 and MT1‐MMP was revealed in tumour cells within an endothelial environment. Furthermore, we found that cell migration through the endothelial ECM was almost totally dependent on αv integrin function, whereas β1 integrins were not solicited. In addition, inhibitors of MMP2 activity (alone or combined with anti‐αv integrin MAb) or TSRI265 (which blocks MMP2‐αvβ3 association) were found to impede this process. Finally, αv integrins, MT1‐MMP and MMP2 were found in ovarian carcinoma cells within the 3‐dimensional architecture of intraperitoneal tumour nodes collected from nude mice xenografted with IGROV1 or SKOV3 cell lines or within human tumour tissues. αv integrins therefore appear as essential to the migration properties of human ovarian carcinoma cells, especially in an endothelial environment, with MMP2 participating to this process.
1 October 2013 in Biochimica et Biophysica Acta (BBA) - General Subjects
Electroactive, elastomeric, microfiber mats that show controllable pore size variation upon electrochemical stimulation are produced from semi-interpenetrating polymer networks (s-IPNs). This type of porous, elastomeric scaffolds that are mechanically dynamic under electrochemical stimuli could find new applications in stretchable electronics, (bio)filtration, soft robotics and stimulation of biological cells. These microfiber mats are prepared in two simple steps. Firstly, a mixture of high molecular weight nitrile butadiene rubber (NBR) and cross-linking agent, poly(ethylene glycol)dimethylacrylate are electrospun with in situ cross-linking. Secondly, a conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) is embedded into the electrospun fibres by oxidative chemical polymerization of EDOT-swollen microfiber mats. This two-step process affords robust, highly flexible and conductive s-IPN microfiber mats. The microfiber mat undergoes a controllable pore size variation upon applying an electrochemical stimulus in the form of a reduction–oxidation cycle to the mats in an electrolyte. The maximum average pore size variation, measured in situ using confocal microscopy, is 25%, achieved in 1 M lithium bis-trifluoromethanesulfonimide (LiTFSI) in propylene carbonate (PC) for a potential step between +0.6 V and −0.5 V (vs. Ag wire). These mats also show pore size variation in a biologically compatible solution, phosphate buffered saline.