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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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/5/1143 |
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| author | Laia Sadeghi Gustav Arvidsson Magali Merrien Agata M. Wasik André Görgens C.I. Edvard Smith Birgitta Sander Anthony P. Wright |
| author_facet | Laia Sadeghi Gustav Arvidsson Magali Merrien Agata M. Wasik André Görgens C.I. Edvard Smith Birgitta Sander Anthony P. Wright |
| author_sort | Laia Sadeghi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T20:04:50Z |
| format | Article |
| id | doaj.art-bf880339b441438eb4264f70fc1446f7 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:04:50Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bf880339b441438eb4264f70fc1446f72023-11-19T23:21:15ZengMDPI AGCancers2072-66942020-05-01125114310.3390/cancers12051143Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal CellsLaia Sadeghi0Gustav Arvidsson1Magali Merrien2Agata M. Wasik3André Görgens4C.I. Edvard Smith5Birgitta Sander6Anthony P. Wright7Department of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, SwedenDepartment of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, SwedenDepartment of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 141 52 Stockholm, SwedenDepartment of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 141 52 Stockholm, SwedenDepartment of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, SwedenDepartment of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, SwedenDepartment of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 141 52 Stockholm, SwedenDepartment of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, SwedenInteractions 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.https://www.mdpi.com/2072-6694/12/5/1143B-cell receptor signalingmantle cell lymphomaibrutinibacalabrutinibCXCR4RNA sequencing |
| spellingShingle | Laia Sadeghi Gustav Arvidsson Magali Merrien Agata M. Wasik André Görgens C.I. Edvard Smith Birgitta Sander Anthony P. Wright Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells Cancers B-cell receptor signaling mantle cell lymphoma ibrutinib acalabrutinib CXCR4 RNA sequencing |
| 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 | B-cell receptor signaling mantle cell lymphoma ibrutinib acalabrutinib CXCR4 RNA sequencing |
| url | https://www.mdpi.com/2072-6694/12/5/1143 |
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