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Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes.
Guilloton F., Caron G., Ménard C., Pangault C., Amé-Thomas P., Dulong J., De Vos J., Rossille D., Henry C., Lamy T. et al
Blood 119, 11 (2012) 2556-67 - http://www.hal.inserm.fr/inserm-00665887
(22289889)
Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes.
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
1 :  Microenvironnement et cancer
INSERM : U917 – Université de Rennes 1 – Biosit
France
2 :  HITC - Service d'Hématologie, Immunologie et de Thérapie Cellulaire
Hôpital Pontchaillou – CHU Rennes – Université de Rennes 1
2 rue Henri Le Guilloux 35033 RENNES cedex 9
France
3 :  IRB - Institut de recherche en biothérapie
CHRU Montpellier – Université Montpellier I
Hôpital Saint-Eloi 34000 Montpellier
France
4 :  Modélisation Conceptuelle des Connaissances Biomédicales
INSERM : U936 – Université de Rennes 1 – Biosit
France
5 :  Service d'hématologie clinique
http://www.chu-rennes.fr/
Hôpital Pontchaillou – Université de Rennes 1
France
6 :  Service de chirurgie thoracique cardiaque et vasculaire [Rennes]
CHU Rennes – Hôpital Pontchaillou – Université de Rennes 1
35033 Rennes
France
CCL2 AND FOLLICULAR LYMPHOMA CELL NICHE
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.
Sciences du Vivant/Immunologie
Anglais
0006-4971

Articles dans des revues avec comité de lecture
10.1182/blood-2011-08-370908
Blood (Blood)
Publisher American Society of Hematology
ISSN 0006-4971 (eISSN : 1528-0020)
internationale
15/03/2012
30/01/2012
119
11
2556-67

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
INCa libre PL06-10; INCa PAIR Lymphome 2008-019; Ligue Régionale Contre le Cancer
Liste des fichiers attachés à ce document : 
PDF
FL_MSC_K_Tarte.pdf(2.1 MB)
ANNEX
Supplemental_data_FL_MSC_KTarte.pdf(5.5 MB)

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