A novel 3D culture model recapitulates primary FL B-cell features and promotes their survival.

Autor:	Lamaison C; Unité Mixte de Recherche (UMR) S1236, University of Rennes, Institut National de la Santé et de la recherche Médicale (INSERM), Etablissement Français du sang, Rennes, France., Latour S; University of Bordeaux, INSERM U1218 ACTION, Centre National de la Recherche Scientifique (CNRS), Bordeaux, France.; Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France., Hélaine N; University of Bordeaux, CNRS UMR 5298 LP2N, Laboratoire Photonique Numérique et Nanosciences, Institut d'Optique Graduate School, Talence, France., Le Morvan V; University of Bordeaux, INSERM U1218 ACTION, Centre National de la Recherche Scientifique (CNRS), Bordeaux, France.; Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France., Saint-Vanne J; Unité Mixte de Recherche (UMR) S1236, University of Rennes, Institut National de la Santé et de la recherche Médicale (INSERM), Etablissement Français du sang, Rennes, France., Mahouche I; University of Bordeaux, INSERM U1218 ACTION, Centre National de la Recherche Scientifique (CNRS), Bordeaux, France.; Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France., Monvoisin C; Unité Mixte de Recherche (UMR) S1236, University of Rennes, Institut National de la Santé et de la recherche Médicale (INSERM), Etablissement Français du sang, Rennes, France., Dussert C; University of Bordeaux, INSERM U1218 ACTION, Centre National de la Recherche Scientifique (CNRS), Bordeaux, France.; Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France., Andrique L; University of Bordeaux, TBMCore VoxCell facility, Bordeaux, France., Deleurme L; Unité Mixte de Recherche (UMR) S1236, University of Rennes, Institut National de la Santé et de la recherche Médicale (INSERM), Etablissement Français du sang, Rennes, France., Dessauge E; Unité Mixte de Recherche (UMR) S1236, University of Rennes, Institut National de la Santé et de la recherche Médicale (INSERM), Etablissement Français du sang, Rennes, France., Pangault C; Unité Mixte de Recherche (UMR) S1236, University of Rennes, Institut National de la Santé et de la recherche Médicale (INSERM), Etablissement Français du sang, Rennes, France.; Pôle de Biologie, Centre Hopsitalo-Universitaire Pontchaillou, Rennes, France., Baulande S; Institut Curie Genomics of Excellence (ICGex) Platform, Institut Curie Research Center, Paris Sciences et Lettres Research University, Paris, France., Legoix P; Institut Curie Genomics of Excellence (ICGex) Platform, Institut Curie Research Center, Paris Sciences et Lettres Research University, Paris, France., Seffals M; University of Rennes, INSERM, CNRS, Unité Mixte de Service Biosit, Core Facility H2P2, Rennes, France; and., Broca-Brisson L; University of Bordeaux, INSERM U1218 ACTION, Centre National de la Recherche Scientifique (CNRS), Bordeaux, France.; Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France., Alessandri K; University of Bordeaux, CNRS UMR 5298 LP2N, Laboratoire Photonique Numérique et Nanosciences, Institut d'Optique Graduate School, Talence, France., Carlotti M; University of Bordeaux, INSERM U1053 BARITON, Bordeaux, France., Soubeyran P; University of Bordeaux, INSERM U1218 ACTION, Centre National de la Recherche Scientifique (CNRS), Bordeaux, France.; Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France., Merlio JP; University of Bordeaux, INSERM U1053 BARITON, Bordeaux, France., Mourcin F; Unité Mixte de Recherche (UMR) S1236, University of Rennes, Institut National de la Santé et de la recherche Médicale (INSERM), Etablissement Français du sang, Rennes, France., Nassoy P; University of Bordeaux, CNRS UMR 5298 LP2N, Laboratoire Photonique Numérique et Nanosciences, Institut d'Optique Graduate School, Talence, France., Recher G; University of Bordeaux, CNRS UMR 5298 LP2N, Laboratoire Photonique Numérique et Nanosciences, Institut d'Optique Graduate School, Talence, France., Tarte K; Unité Mixte de Recherche (UMR) S1236, University of Rennes, Institut National de la Santé et de la recherche Médicale (INSERM), Etablissement Français du sang, Rennes, France.; Pôle de Biologie, Centre Hopsitalo-Universitaire Pontchaillou, Rennes, France., Bresson-Bepoldin L; University of Bordeaux, INSERM U1218 ACTION, Centre National de la Recherche Scientifique (CNRS), Bordeaux, France.; Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2021 Dec 14; Vol. 5 (23), pp. 5372-5386.
DOI:	10.1182/bloodadvances.2020003949
Abstrakt:	Non-Hodgkin B-cell lymphomas (B-NHL) mainly develop within lymph nodes as aggregates of tumor cells densely packed with their surrounding microenvironment, creating a tumor niche specific to each lymphoma subtypes. In vitro preclinical models mimicking biomechanical forces, cellular microenvironment, and 3D organization of B-cell lymphomas remain scarce, while all these parameters are key determinants of lymphomagenesis and drug resistance. Using a microfluidic method based on cell encapsulation inside permeable, elastic, and hollow alginate microspheres, we developed a new tunable 3D model incorporating lymphoma B cells, extracellular matrix (ECM), and/or tonsil stromal cells (TSC). Under 3D confinement, lymphoma B cells were able to form cohesive spheroids resulting from overexpression of ECM components. Moreover, lymphoma B cells and TSC dynamically formed self-organized 3D spheroids favoring tumor cell growth. 3D culture induced resistance to the classical chemotherapeutic agent doxorubicin, but not to the BCL2 inhibitor ABT-199, identifying this approach as a relevant in vitro model to assess the activity of therapeutic agents in B-NHL. RNA-sequence analysis highlighted the synergy of 3D, ECM, and TSC in upregulating similar pathways in malignant B cells in vitro than those overexpressed in primary lymphoma B cells in situ. Finally, our 3D model including ECM and TSC allowed long-term in vitro survival of primary follicular lymphoma B cells. In conclusion, we propose a new high-throughput 3D model mimicking lymphoma tumor niche and making it possible to study the dynamic relationship between lymphoma B cells and their microenvironment and to screen new anti-cancer drugs. (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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