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Series GSE122739 Query DataSets for GSE122739
Status Public on Sep 09, 2021
Title Differential requirement for B-cell Receptor signaling during adhesion of different Mantle Cell Lymphoma cell lines to stromal cells
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Lymphoma cells interact with specific microenvironment cell subsets, such as stromal cells, from which they receive survival and proliferation stimuli. These interactions negatively influence therapeutic response and increase the risk for drug resistance and relapse. It is still not clear why clinically similar tumors in different patients respond differently to established treatment regimens. Objective: The main aim of this study was to identify and compare key signaling pathways related to stromal cell adhesion in different mantle cell lymphoma (MCL) cell lines.Methods: Human MCL cells (JeKo1 and REC1) were cultured alone or in co-culture with mouse MS-5 stromal cells. Differentially expressed genes in adherent cells were identified by RNA sequencing and species-specific read sorting. The cell surface levels of proteins encoded by selected differentially expressed genes were quantified using flow cytometry in adherent and suspension cells. Selective inhibitors or siRNA were used to assess their significance for adherence to stromal cells. Results: Jeko1 and REC1 cells exhibited different time-dependent patterns of adhesion to stromal cells. 590 genes that were differently regulated upon adhesion in each cell line individually, showed significant differences in the extent or direction of regulation between the two cell lines. From this set, there was a significant increase in transcript levels for B-cell Receptor (BCR) pathway signature genes in adherent JeKo1 cell but not in adherent REC1 cells. Inhibition of BCR signaling using siRNA or the clinically approved inhibitor, Ibrutinib, decreased the number of adherent JeKo1 cells but had no such effect on REC1 cells. The cell surface levels of CXCR4 were higher in JeKo1 cells compared to REC1 cells and CXCR4 inhibition disrupted the adhesion of JeKo1 but not REC1 cells to the stromal cells. ICAM1 cell surface levels were induced in JeKo1 cells upon adhesion while REC1 showed a high level of ICAM1 in non-adherent cells. Depletion of ICAM1 levels by siRNA reduced the stromal cell adhesion of both JeKo1 and REC1 cells. Conclusions: The results suggest that different MCL cell lines exhibit different signaling profiles and pathway dependencies during microenvironment interaction. In this study BCR signaling pathways were shown to be important for stromal cell adhesion of JeKo1 cells but not REC1 cells. This provides a possible mechanism to account for the differential responsiveness of MCL patients to treatment with the Bruton’s Tyrosine Kinase inhibitor, Ibrutinib, an inhibitor of BCR signaling that is clinically approved for MCL.
Overall design RNA-seq; four conditions with four replicates per condition, 16 samples in total.
Contributor(s) Arvidsson G, Wright A, Sadeghi L
Citation(s) 32370190
Submission date Nov 20, 2018
Last update date Sep 09, 2021
Contact name Gustav Arvidsson
Organization name Uppsala Universitet
Department Department of Medical Sciences
Street address Husargatan 3
City Uppsala
State/province Uppsala
ZIP/Postal code SE-752 37
Country Sweden
Platforms (3)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL22245 Illumina HiSeq 2500 (Homo sapiens; Mus musculus)
Samples (16)
GSM3484411 MS-5_1; Sample_5A
GSM3484412 SEP_1; Sample_5B
GSM3484413 ADH_1; Sample_5C
BioProject PRJNA506213
SRA SRP169865

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Supplementary file Size Download File type/resource
GSE122739_GRCh38_featurecounts_count_table.csv.gz 1.2 Mb (ftp)(http) CSV
GSE122739_GRCm38_featurecounts_count_table.csv.gz 841.9 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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