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Compact spheroid formation by ovarian cancer cells is associated with contractile behavior and an invasive phenotype
Author(s) -
Sodek Katharine L.,
Ringuette Maurice J.,
Brown Theodore J.
Publication year - 2009
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.24188
Subject(s) - spheroid , phenotype , ovarian cancer , biology , cancer , cancer research , pathology , microbiology and biotechnology , medicine , cell culture , genetics , gene
Abstract Ovarian cancer cells are present in malignant ascites both as individual cells and as multicellular spheroid aggregates. Although spheroid formation affords protection of cancer cells against some chemotherapeutic agents, it has not been established whether a relationship exists between invasive behavior and predisposition to spheroid formation. Aspects of spheroid formation, including cell‐matrix adhesion, remodeling and contractility are characteristic myofibroblast‐like behaviors associated with fibrosis that contribute to tumor growth and dissemination. We explored the possibility that cell behaviors that promote spheroid formation also facilitate invasion. Our analysis of 6 human ovarian cancer cell lines indicated that ovarian cancer cells possessing myofibroblast‐like properties formed compact spheroids and invaded 3D matrices. These cells readily contracted collagen I gels, possessed a spindle‐like morphology, and had elevated expression of genes associated with the TGFβ‐mediated fibrotic response and/or β1 integrin function, including fibronectin (FN), connective tissue growth factor (CTGF/CCN2), lysyl oxidase (LOX1), tissue transglutaminase 2 (TGM2) and urinary plasminogen activator receptor (uPAR). Whereas cell aggregation was induced by TGFβ, and by β1‐integrin overexpression and activation, these treatments did not stimulate the contractile activity required for spheroid compaction. The positive relationship found between compact spheroid formation and invasive behavior implies a preferential survival of an invasive subpopulation of ovarian cancer cells, as cells in spheroids are more resistant to several chemotherapeutics. Preventing the formation of ovarian cancer spheroids may represent a novel strategy to improve the efficacy of existing therapeutics. © 2008 Wiley‐Liss, Inc.