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Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells

Interactions between lymphoma cells and stromal cells play a key role in promoting tumor survival and development of drug resistance. We identified differences in key signaling pathways between the JeKo-1 and REC-1 mantle cell lymphoma (MCL) cell lines, displaying different patterns of stromal cell...

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Autores principales: Sadeghi, Laia, Arvidsson, Gustav, Merrien, Magali, Wasik, Agata M., Görgens, André, Smith, C.I. Edvard, Sander, Birgitta, P. Wright, Anthony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281289/
https://www.ncbi.nlm.nih.gov/pubmed/32370190
http://dx.doi.org/10.3390/cancers12051143
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author Sadeghi, Laia
Arvidsson, Gustav
Merrien, Magali
Wasik, Agata M.
Görgens, André
Smith, C.I. Edvard
Sander, Birgitta
P. Wright, Anthony
author_facet Sadeghi, Laia
Arvidsson, Gustav
Merrien, Magali
Wasik, Agata M.
Görgens, André
Smith, C.I. Edvard
Sander, Birgitta
P. Wright, Anthony
author_sort Sadeghi, Laia
collection PubMed
description Interactions between lymphoma cells and stromal cells play a key role in promoting tumor survival and development of drug resistance. We identified differences in key signaling pathways between the JeKo-1 and REC-1 mantle cell lymphoma (MCL) cell lines, displaying different patterns of stromal cell adhesion and chemotaxis towards stroma-conditioned medium. The identified adhesion-regulated genes reciprocated important aspects of microenvironment-mediated gene modulation in MCL patients. Five-hundred and ninety genes were differently regulated between the cell lines upon adhesion to stromal cells, while 32 genes were similarly regulated in both cell lines. Regulation of B-cell Receptor (BCR) signature genes in adherent cells was specific for JeKo-1. Inhibition of BCR using siRNA or clinically approved inhibitors, Ibrutinib and Acalabrutinib, decreased adhesion of JeKo-1, but not REC-1 cells. Cell surface levels of chemokine receptor CXCR4 were higher in JeKo-1, facilitating migration and adhesion of JeKo-1 but not REC-1 cells. Surface levels of ICAM1 adhesion protein differ for REC-1 and JeKo-1. While ICAM1 played a positive role in adherence of both cell lines to stromal cells, S1PR1 had an inhibitory effect. Our results provide a model framework for further investigation of mechanistic differences in patient-response to new pathway-specific drugs.
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spelling pubmed-72812892020-06-19 Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells Sadeghi, Laia Arvidsson, Gustav Merrien, Magali Wasik, Agata M. Görgens, André Smith, C.I. Edvard Sander, Birgitta P. Wright, Anthony Cancers (Basel) Article Interactions between lymphoma cells and stromal cells play a key role in promoting tumor survival and development of drug resistance. We identified differences in key signaling pathways between the JeKo-1 and REC-1 mantle cell lymphoma (MCL) cell lines, displaying different patterns of stromal cell adhesion and chemotaxis towards stroma-conditioned medium. The identified adhesion-regulated genes reciprocated important aspects of microenvironment-mediated gene modulation in MCL patients. Five-hundred and ninety genes were differently regulated between the cell lines upon adhesion to stromal cells, while 32 genes were similarly regulated in both cell lines. Regulation of B-cell Receptor (BCR) signature genes in adherent cells was specific for JeKo-1. Inhibition of BCR using siRNA or clinically approved inhibitors, Ibrutinib and Acalabrutinib, decreased adhesion of JeKo-1, but not REC-1 cells. Cell surface levels of chemokine receptor CXCR4 were higher in JeKo-1, facilitating migration and adhesion of JeKo-1 but not REC-1 cells. Surface levels of ICAM1 adhesion protein differ for REC-1 and JeKo-1. While ICAM1 played a positive role in adherence of both cell lines to stromal cells, S1PR1 had an inhibitory effect. Our results provide a model framework for further investigation of mechanistic differences in patient-response to new pathway-specific drugs. MDPI 2020-05-02 /pmc/articles/PMC7281289/ /pubmed/32370190 http://dx.doi.org/10.3390/cancers12051143 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sadeghi, Laia
Arvidsson, Gustav
Merrien, Magali
Wasik, Agata M.
Görgens, André
Smith, C.I. Edvard
Sander, Birgitta
P. Wright, Anthony
Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells
title Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells
title_full Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells
title_fullStr Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells
title_full_unstemmed Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells
title_short Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells
title_sort differential b-cell receptor signaling requirement for adhesion of mantle cell lymphoma cells to stromal cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281289/
https://www.ncbi.nlm.nih.gov/pubmed/32370190
http://dx.doi.org/10.3390/cancers12051143
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