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

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...

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Autores principales: Lamaison, Claire, Latour, Simon, Hélaine, Nelson, Le Morvan, Valérie, Saint-Vanne, Julien, Mahouche, Isabelle, Monvoisin, Céline, Dussert, Christelle, Andrique, Laëtitia, Deleurme, Laurent, Dessauge, Elise, Pangault, Céline, Baulande, Sylvain, Legoix, Patricia, Seffals, Marine, Broca-Brisson, Léa, Alessandri, Kévin, Carlotti, Martina, Soubeyran, Pierre, Merlio, Jean-Philippe, Mourcin, Frédéric, Nassoy, Pierre, Recher, Gaëlle, Tarte, Karin, Bresson-Bepoldin, Laurence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9153016/
https://www.ncbi.nlm.nih.gov/pubmed/34555842
http://dx.doi.org/10.1182/bloodadvances.2020003949
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author Lamaison, Claire
Latour, Simon
Hélaine, Nelson
Le Morvan, Valérie
Saint-Vanne, Julien
Mahouche, Isabelle
Monvoisin, Céline
Dussert, Christelle
Andrique, Laëtitia
Deleurme, Laurent
Dessauge, Elise
Pangault, Céline
Baulande, Sylvain
Legoix, Patricia
Seffals, Marine
Broca-Brisson, Léa
Alessandri, Kévin
Carlotti, Martina
Soubeyran, Pierre
Merlio, Jean-Philippe
Mourcin, Frédéric
Nassoy, Pierre
Recher, Gaëlle
Tarte, Karin
Bresson-Bepoldin, Laurence
author_facet Lamaison, Claire
Latour, Simon
Hélaine, Nelson
Le Morvan, Valérie
Saint-Vanne, Julien
Mahouche, Isabelle
Monvoisin, Céline
Dussert, Christelle
Andrique, Laëtitia
Deleurme, Laurent
Dessauge, Elise
Pangault, Céline
Baulande, Sylvain
Legoix, Patricia
Seffals, Marine
Broca-Brisson, Léa
Alessandri, Kévin
Carlotti, Martina
Soubeyran, Pierre
Merlio, Jean-Philippe
Mourcin, Frédéric
Nassoy, Pierre
Recher, Gaëlle
Tarte, Karin
Bresson-Bepoldin, Laurence
author_sort Lamaison, Claire
collection PubMed
description 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.
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spelling pubmed-91530162022-05-31 A novel 3D culture model recapitulates primary FL B-cell features and promotes their survival Lamaison, Claire Latour, Simon Hélaine, Nelson Le Morvan, Valérie Saint-Vanne, Julien Mahouche, Isabelle Monvoisin, Céline Dussert, Christelle Andrique, Laëtitia Deleurme, Laurent Dessauge, Elise Pangault, Céline Baulande, Sylvain Legoix, Patricia Seffals, Marine Broca-Brisson, Léa Alessandri, Kévin Carlotti, Martina Soubeyran, Pierre Merlio, Jean-Philippe Mourcin, Frédéric Nassoy, Pierre Recher, Gaëlle Tarte, Karin Bresson-Bepoldin, Laurence Blood Adv Lymphoid Neoplasia 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. American Society of Hematology 2021-12-09 /pmc/articles/PMC9153016/ /pubmed/34555842 http://dx.doi.org/10.1182/bloodadvances.2020003949 Text en © 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.
spellingShingle Lymphoid Neoplasia
Lamaison, Claire
Latour, Simon
Hélaine, Nelson
Le Morvan, Valérie
Saint-Vanne, Julien
Mahouche, Isabelle
Monvoisin, Céline
Dussert, Christelle
Andrique, Laëtitia
Deleurme, Laurent
Dessauge, Elise
Pangault, Céline
Baulande, Sylvain
Legoix, Patricia
Seffals, Marine
Broca-Brisson, Léa
Alessandri, Kévin
Carlotti, Martina
Soubeyran, Pierre
Merlio, Jean-Philippe
Mourcin, Frédéric
Nassoy, Pierre
Recher, Gaëlle
Tarte, Karin
Bresson-Bepoldin, Laurence
A novel 3D culture model recapitulates primary FL B-cell features and promotes their survival
title A novel 3D culture model recapitulates primary FL B-cell features and promotes their survival
title_full A novel 3D culture model recapitulates primary FL B-cell features and promotes their survival
title_fullStr A novel 3D culture model recapitulates primary FL B-cell features and promotes their survival
title_full_unstemmed A novel 3D culture model recapitulates primary FL B-cell features and promotes their survival
title_short A novel 3D culture model recapitulates primary FL B-cell features and promotes their survival
title_sort novel 3d culture model recapitulates primary fl b-cell features and promotes their survival
topic Lymphoid Neoplasia
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9153016/
https://www.ncbi.nlm.nih.gov/pubmed/34555842
http://dx.doi.org/10.1182/bloodadvances.2020003949
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