%0 Journal Article
%T Collagen I but not Matrigel matrices provide an MMP-dependent barrier to ovarian cancer cell penetration
%A Katharine L Sodek
%A Theodore J Brown
%A Maurice J Ringuette
%J BMC Cancer
%D 2008
%I BioMed Central
%R 10.1186/1471-2407-8-223
%X The requirement of MMP activity for ovarian cancer cell penetration of Matrigel and collagen matrices was assessed in 2D transwell and 3D spheroid culture systems.The broad range MMP inhibitor GM6001 completely prevented cell perforation of polymerised collagen I-coated transwell membranes. In contrast, GM6001 decreased ES-2 cell penetration of Matrigel by only ~30% and had no effect on HEY cell Matrigel penetration. In 3D culture, ovarian cancer cells grown as spheroids also migrated into surrounding Matrigel matrices despite MMP blockade. In contrast, MMP activity was required for invasion into 3D matrices of collagen I reconstituted from acid-soluble rat-tail collagen I, but not from pepsin-extracted collagen I (Vitrogen/Purecol), which lacks telopeptide regions.Matrigel does not form representative barriers to ovarian cancer cells in either 2D or 3D culture systems. Our findings support the use of collagen I rather than Matrigel as a matrix barrier for invasion studies to better approximate critical interactions and events associated with peritoneal metastasis.Cancer cell invasion of tissue matrices is a fundamental aspect of metastasis. Extracellular matrices (ECM) are generally considered to be of two types, basement membrane and stromal/interstitial. Basement membrane matrices are normally deposited beneath epithelia, and its components characteristically include collagen IV, laminin, perlecan and nidogen, which interact to form a thin, dense, cross-linked polymeric network with high tensile strength. Stromal/interstitial matrices form the majority of the body connective tissue and are composed primarily of fibrillar collagen I that is cross-linked into a stable meshwork to impart 3D structural support. As both basement membrane and stromal matrices present a steric barrier to cell transmigration, matrix remodelling is a necessary and critical contributor to metastasis. Tumour cells acquire the ability to surmount ECM barriers by expressing a range of proteas
%U http://www.biomedcentral.com/1471-2407/8/223