PMID: identifiant de la référence Pubmed : |
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(22289889) |
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| titre : |
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Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes. |
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| auteur(s) : |
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Fabien Guilloton1, Gersende Caron1, 2, Cédric Ménard1, 2, Céline Pangault1, 2, Patricia Amé-Thomas1, 2, Joëlle Dulong1, John De Vos3, Delphine Rossille4, Catherine Henry2, Thierry Lamy1, 5, Olivier Fouquet6, Thierry Fest1, 2, Karin Tarte ( ) 1, 2 |
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| laboratoire : |
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| titre abrégé : |
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CCL2 AND FOLLICULAR LYMPHOMA CELL NICHE |
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| résumé : |
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Accumulating evidence indicates that infiltrating stromal cells contribute directly and indirectly to tumor growth in a wide range of cancers. In follicular lymphoma (FL), malignant B cells are found admixed with heterogeneous lymphoid-like stromal cells within invaded lymph nodes and BM. In addition, mesenchymal stromal cells (MSCs) support in vitro FL B-cell survival, in particular after their engagement toward lymphoid differentiation. We show here that BM-MSCs obtained from patients with FL (FL-MSCs) display a specific gene expression profile compared with MSCs obtained from healthy age-matched donors (HD-MSCs). This FL-MSC signature is significantly enriched for genes associated with a lymphoid-like commitment. Interestingly, CCL2 could be detected at a high level within the FL-cell niche, is up-regulated in HD-MSCs by coculture with malignant B cells, and is overexpressed by FL-MSCs, in agreement with their capacity to recruit monocytes more efficiently than HD-MSCs. Moreover, FL-MSCs and macrophages cooperate to sustain malignant B-cell growth, whereas FL-MSCs drive monocyte differentiation toward a proangiogenic and lipopolysaccharide-unresponsive phenotype close to that of tumor-associated macrophages. Altogether, these results highlight the complex role of FL stromal cells that promote direct tumor B-cell growth and orchestrate FL-cell niche, thus emerging as a potential therapeutic target in this disease. |
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| domaine : |
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Sciences du Vivant/Immunologie
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langue du texte intégral : |
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Anglais |
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| ISSN : |
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0006-4971 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1182/blood-2011-08-370908 |
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| journal : |
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| Blood (Blood) |
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American Society of Hematology |
| ISSN |
0006-4971 (eISSN : 1528-0020) |
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| Audience : |
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internationale |
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| date de publication : |
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15/03/2012 |
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date de publication électronique : |
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30/01/2012 |
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| volume : |
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119 |
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| numéro : |
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11 |
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| page, identifiant, ... : |
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2556-67 |
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| Descripteur(s) MeSH : |
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Adult – Aged – B-Lymphocytes – Blotting – Western – Cell Differentiation – Cell Movement – Cell Polarity – Cell Proliferation – Cells – Cultured – Chemokine CCL2 – Female – Gene Expression Profiling – Humans – Lymphoma – Follicular – Male – Mesenchymal Stem Cells – Middle Aged – Monocytes – Oligonucleotide Array Sequence Analysis – RNA – Messenger – Real-Time Polymerase Chain Reaction – Stromal Cells – Tumor Markers – Biological |
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| contrat, financement : |
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INCa libre PL06-10; INCa PAIR Lymphome 2008-019; Ligue Régionale Contre le Cancer |
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