title: Differential expressions of adhesive molecules and proteases define mechanisms of ovarian tumor cell matrix penetration/invasion.
abstract: Epithelial ovarian cancer is an aggressive and deadly disease and understanding its invasion mechanisms is critical for its treatment. We sought to study the penetration/invasion of ovarian tumor cells into extracellular matrices (ECMs) using a fibroblast-derived three-dimensional (3D) culture model and time-lapse and confocal imaging. Twelve ovarian tumor cells were evaluated and classified into distinct groups based on their ECM remodeling phenotypes; those that degraded the ECM (represented by OVCAR5 cells) and those that did not (represented by OVCAR10 cells). Cells exhibiting a distinct ECM modifying behavior were also segregated by epithelial- or mesenchymal-like phenotypes and uPA or MMP-2/MMP-9 expression. The cells, which presented epithelial-like phenotypes, penetrated the ECM using proteases and maintained intact cell-cell interactions, while cells exhibiting mesenchymal phenotypes modified the matrices via Rho-associated serine/threonine kinase (ROCK) in the absence of apparent cell-cell interactions. Overall, this study demonstrates that different mechanisms of modifying matrices by ovarian tumor cells may reflect heterogeneity among tumors and emphasize the need to systematically assess these mechanisms to better design effective therapies.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
authors.forename: Edna
authors.initials: E
authors.lastname: Cukierman
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002364:Caseins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D009928:Organ Specificity / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010641:Phenotype; D011480:Protease Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013997:Time Factors; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002364:Caseins; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; D005780:Gelatin; D054460:rho-Associated Kinases; D010447:Peptide Hydrolases