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Differential B-Cell...
Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells
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- Sadeghi, L (författare)
- Karolinska Institutet
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Arvidsson, G (författare)
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- Merrien, M (författare)
- Karolinska Institutet
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- Wasik, AM (författare)
- Karolinska Institutet
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- Gorgens, A (författare)
- Karolinska Institutet
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- Smith, CIE (författare)
- Karolinska Institutet
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- Sander, B (författare)
- Karolinska Institutet
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- Wright, AP (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2020-05-02
- 2020
- Engelska.
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:5
- Relaterad länk:
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https://www.mdpi.com...
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http://kipublication...
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https://doi.org/10.3...
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Abstract
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- 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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- art (ämneskategori)
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Cancers
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