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Initial formation of IGROV1 ovarian cancer multicellular aggregates involves vitronectin

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Tumor Biology

Abstract

Ovarian cancer progression is frequently associated with the development of malignant ascites. Multicellular aggregates of carcinoma cells (spheroids) found within ascites are thought to be able to promote peritoneal carcinomatosis. We have previously demonstrated the involvement of the vitronectin/αv integrin adhesive system in the dissemination of ovarian cancer cells and continue to investigate the influence of these molecules by studying their role(s) in spheroid behavior. The aim of this study was to generate ovarian cancer multicellular aggregates and to focus on the role of vitronectin and αv integrins in their initiation. IGROV1 cancer cells cultured in the absence of adhesive substratum formed multicellular aggregates comparable to spheroids. After 21 days, a fraction of the cells within clusters remained viable and proliferated recurrently. Within the multicellular aggregates, vitronectin and αv integrins were co-localized at intercellular sites, suggesting their involvement in cell-cell interactions. Initial formation of IGROV1 aggregates was inhibited using anti-vitronectin and anti-αv integrin blocking antibodies or the cyclic peptide cRGDfV. Vitronectin expression persisted during cluster disaggregation on fibronectin. These results demonstrate the ability of IGROV1 cells to generate multicellular aggregates and point to a contributory role for the vitronectin/αv integrin system in the initial step of this process. These events could represent a prerequisite for further dissemination.

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Acknowledgments

We thank Pr JF Héron, oncogynecologist of the Centre F. Baclesse (CFB) and Dr F. Morvan, head of the oncology service of the Centre R. Dubos (CRD) for their constant support. This work was supported by the Ligue Contre le Cancer (Comité du Val d’Oise) and the University of Cergy-Pontoise. We thank C. Blanc-Fournier (CFB), V. Villefranques (CRD) for providing ascites I. Zimmerman (UMR CNRS 6143) for his technical support in scanning microscopy and M. Duval (plateforme cytométrie, IFR 146 ICORE). J. Fernandes is the recipient of a fellowship from the Ligue Contre le Cancer (Comité du Val d’Oise).

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Authors and Affiliations

  1. ERRMECe, EA 1391, Institut des materiaux, UFR Sciences et Techniques, Université de Cergy Pontoise, 2 rue Adolphe Chauvin, 95302, Cergy-Pontoise Cedex, France

    Sabrina Kellouche, Julien Fernandes, Johanne Leroy-Dudal, Olivier Gallet & Franck Carreiras

  2. Unité Biologie et Thérapies Innovantes des Cancers Localement Agressifs, Groupe Régional d’Etudes sur le Cancer, EA 1772 et IFR ICORE 146, Université de Caen-Basse Normandie et Centre de Lutte Contre le Cancer F. Baclesse, Caen, France

    Soizic Dutoit & Laurent Poulain

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  1. Sabrina Kellouche
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  2. Julien Fernandes
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  3. Johanne Leroy-Dudal
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Correspondence to Franck Carreiras.

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Ligue Contre le Cancer (Comité du Val d’Oise) and Cergy-Pontoise University

Sabrina Kellouche and Julien Fernandes contributed equally to this work.

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Kellouche, S., Fernandes, J., Leroy-Dudal, J. et al. Initial formation of IGROV1 ovarian cancer multicellular aggregates involves vitronectin. Tumor Biol. 31, 129–139 (2010). https://doi.org/10.1007/s13277-010-0017-9

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  • DOI: https://doi.org/10.1007/s13277-010-0017-9

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