Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis.
Accumulating evidence indicates that the cellular microenvironment plays a key role in follicular lymphoma (FL) pathogenesis, both within tumor lymph nodes (LNs) and in infiltrated bone marrow where ectopic LN-like reticular cells are integrated within malignant B-cell nodular aggregates. In normal secondary lymphoid organs, specific stromal cell subsets provide a highly specialized microenvironment that supports immune response. In particular, fibroblastic reticular cells (FRCs) mediate immune cell migration, adhesion, and reciprocal interactions. The role of FRCs and their postulated progenitors, that is, bone marrow mesenchymal stem cells (MSCs), in FL remains unexplored. In this study, we investigated the relationships between FRCs and MSCs and their capacity to sustain malignant B-cell growth. Our findings strongly suggest that secondary lymphoid organs contain MSCs able to give rise to adipocytes, chondrocytes, osteoblasts, as well as fully functional B-cell supportive FRCs. In vitro, bone marrow-derived MSCs acquire a complete FRC phenotype in response to a combination of tumor necrosis factor-alpha and lymphotoxin-alpha1beta2. Moreover, MSCs recruit primary FL cells that, in turn, trigger their differentiation into FRCs, making them able to support malignant B-cell survival. Altogether, these new insights into the cross talk between lymphoma cells and their microenvironment could offer original therapeutic strategies.
Amé-Thomas
Patricia
P
Unité Propre de Recherche de l'Enseignement Superieur Equipe d'Accueil 3889, Faculté de médicine, Université Rennes 1, and Département Hématologie-Immunologie et Thérapie Cellulaire, Centre Hospitalo-Universitaire Pontchaillou, France.
Maby-El Hajjami
Hélène
H
Monvoisin
Céline
C
Jean
Rachel
R
Monnier
Delphine
D
Caulet-Maugendre
Sylvie
S
Guillaudeux
Thierry
T
Lamy
Thierry
T
Fest
Thierry
T
Tarte
Karin
K
D001854:Bone Marrow Cells / Q000166:cytology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D006801:Humans; D008221:Lymphoid Tissue / Q000166:cytology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000276:immunology* / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D014066:Palatine Tonsil / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*