PMID- 32370190 OWN - NLM STAT- PubMed-not-MEDLINE VI - 12 IP - 5 TI - Differential B-Cell Receptor Signaling Requirement for Adhesion of Mantle Cell Lymphoma Cells to Stromal Cells. LA - eng PT - Journal Article PL - Switzerland TA - Cancers (basel) JT - Cancers JID - 101526829 IS - 2072-6694 (Print) LID - E1143 [pii] LID - 10.3390/cancers12051143 [doi] FAU - Sadeghi, Laia AU - Sadeghi L AD - Department of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, Sweden. FAU - Arvidsson, Gustav AU - Arvidsson G AD - Department of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, Sweden. FAU - Merrien, Magali AU - Merrien M AD - Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 141 52 Stockholm, Sweden. FAU - M Wasik, Agata AU - M Wasik A AD - Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 141 52 Stockholm, Sweden. FAU - Görgens, André AU - Görgens A AD - Department of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, Sweden. AD - Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg, 45 147 Essen, Germany. FAU - Smith, C I Edvard AU - Smith CIE AD - Department of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, Sweden. FAU - Sander, Birgitta AU - Sander B AD - Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, 141 52 Stockholm, Sweden. FAU - Wright, Anthony P AU - Wright AP AD - Department of Laboratory Medicine, Division of Biomedical and Cellular Medicine, Karolinska Institutet, 141 57 Stockholm, Sweden. IS - 2072-6694 (Linking) OTO - NOTNLM OT - B-cell receptor signaling OT - BTK OT - CXCR4 OT - ICAM1 OT - RNA sequencing OT - S1PR1 OT - acalabrutinib OT - coculture OT - ibrutinib OT - mantle cell lymphoma PMC - PMC7281289 LR - 20200928 DP - 2020 May 02 DEP - 20200502 AB - 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.