Premium
Transmigration of human ovarian adenocarcinoma cells through endothelial extracellular matrix involves αv integrins and the participation of MMP2
Author(s) -
LeroyDudal Johanne,
Demeilliers Christine,
Gallet Olivier,
Pauthe Emmanuel,
Dutoit Soizic,
Agniel Rémy,
Gauduchon Pascal,
Carreiras Franck
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20778
Subject(s) - mmp2 , integrin , ovarian carcinoma , extracellular matrix , biology , matrigel , microbiology and biotechnology , cancer research , fibronectin , cell culture , laminin , ovarian cancer , endothelial stem cell , angiogenesis , cell , cancer , metastasis , in vitro , biochemistry , genetics
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. © 2004 Wiley‐Liss, Inc.