Invading basement membrane matrix is sufficient for MDA-MB-231 breast cancer cells to develop a stable in vivo metastatic phenotype
2011
Abdelkarim , Mohamed (Université Paris-Nord (Paris 13)Institut National de la Sante et de la Recherche Medicale, BobignyParis(France). Laboratoire de Chimie Structurale BiomoléculaireINSERM 553 Endothélium et Angiogénèse Laboratoire d’Hémostase) | Vintonenko , Nadejda (Université Paris-Nord (Paris 13)Institut National de la Sante et de la Recherche Medicale, BobignyParis(France). Laboratoire de Chimie Structurale BiomoléculaireINSERM 553 Endothélium et Angiogénèse Laboratoire d’Hémostase) | Starzec , Anna (Université Paris-Nord (Paris 13), Bobigny(France). EA4222, Li2P) | Robles , Aniela (Université Paris-Nord (Paris 13)Université Paris 7, BobignyParis(France). Laboratoire de Chimie Structurale BiomoléculaireUMRS 940. Equipe Avenir, IGM) | Aubert , Julie (INRA , Paris (France). UMR 0518 Mathématiques et Informatique Appliquées) | Martin-Magniette , Marie-Laure (INRA , EvryParis (France). UMRUMR 11650518 Génomique VégétaleMathématiques et Informatique Appliquées) | Moura , Samia (Université Paris 7, Paris(France). UMRS 940. Equipe Avenir, IGM) | Podgorniak , Marie-Pierre (Université Paris 7, Paris(France). UMRS 940. Equipe Avenir, IGM) | Rodrigues-Ferreira , Sylvie ( Institut National de la Santé et de la Recherche MédicaleCentre National de la Recherche Scientifique, Paris Paris(France). U1016UMR8104 Institut Cochin) | Nahmias , Clara ( Institut National de la Santé et de la Recherche MédicaleCentre National de la Recherche Scientifique, Paris Paris(France). U1016UMR8104 Institut Cochin) | Couraud , Pierre-Olivier ( Institut National de la Santé et de la Recherche MédicaleCentre National de la Recherche Scientifique, Paris Paris(France). U1016UMR8104 Institut Cochin) | Doliger , Christelle (Hôpital Saint Louis, Paris(France). Service Commun d’Imagerie, Institut d’Hématologie) | Sainte-Catherine , Odile (Université Paris-Nord (Paris 13), Bobigny(France). Laboratoire de Chimie Structurale Biomoléculaire) | Peyri , Nicole (Université Paris-Nord (Paris 13)Université Paris 7, BobignyParis(France). Laboratoire de Chimie Structurale BiomoléculaireUMRS 940. Equipe Avenir, IGM) | Chen , Lei ( Institut National de la Santé et de la Recherche Médicale, Paris (France). INSERM 553 Endothélium et Angiogénèse Laboratoire d’Hémostase) | Mariau , Jérémie ( Institut National de la Santé et de la Recherche Médicale, Paris (France). INSERM 553 Endothélium et Angiogénèse Laboratoire d’Hémostase) | Etienne , Monique (Université Paris-Nord (Paris 13), Bobigny(France). Laboratoire d’Histologie) | Perret , Gerard-Yves (Université Paris-Nord (Paris 13), Bobigny(France). EA4222, Li2P) | Crepin , Michel ( Institut National de la Santé et de la Recherche Médicale, Paris (France). INSERM 553 Endothélium et Angiogénèse Laboratoire d’Hémostase) | Poyet , Jean-Luc (Université Paris 7, Paris(France). UMRS 940. Equipe Avenir, IGM) | Khatib , Abdel-Majid (Université Paris 7, Paris(France). UMRS 940. Equipe Avenir, IGM) | Di Benedetto , Mélanie (auteur de correspondance) (Université Paris-Nord (Paris 13)Université Paris 7, BobignyParis(France). Laboratoire de Chimie Structurale BiomoléculaireUMRS 940. Equipe Avenir, IGM)
Introduction: The poor efficacy of various anti-cancer treatments against metastatic cells has focused attention on the role of tumor microenvironment in cancer progression. To understand the contribution of the extracellular matrix (ECM) environment to this phenomenon, we isolated ECM surrogate invading cell populations from MDA-MB-231 breast cancer cells and studied their genotype and malignant phenotype. Methods: We isolated invasive subpopulations (INV) from non invasive populations (REF) using a 2D-Matrigel assay, a surrogate of basal membrane passage. INV and REF populations were investigated by microarray assay and for their capacities to adhere, invade and transmigrate in vitro, and to form metastases in nude mice. Results: REF and INV subpopulations were stable in culture and present different transcriptome profiles. INV cells were characterized by reduced expression of cell adhesion and cell-cell junction genes (44% of down regulated genes) and by a gain in expression of anti-apoptotic and pro-angiogenic gene sets. In line with this observation, in vitro INV cells showed reduced adhesion and increased motility through endothelial monolayers and fibronectin. When injected into the circulation, INV cells induced metastases formation, and reduced injected mice survival by up to 80% as compared to REF cells. In nude mice, INV xenografts grew rapidly inducing vessel formation and displaying resistance to apoptosis. Conclusion: Our findings reveal that the in vitro ECM microenvironment per se was sufficient to select for tumor cells with a stable metastatic phenotype in vivo characterized by loss of adhesion molecules expression and induction of proangiogenic and survival factors.
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