Cancers | |
Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells | |
Anthony P. Wright1  C.I. Edvard Smith1  Laia Sadeghi1  André Görgens1  Gustav Arvidsson1  Magali Merrien2  Birgitta Sander2  Agata M.Wasik2  | |
[1] Department of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, Sweden;Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 141 52 Stockholm, Sweden; | |
关键词: B-cell receptor signaling; mantle cell lymphoma; ibrutinib; acalabrutinib; CXCR4; RNA sequencing; | |
DOI : 10.3390/cancers12051143 | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown