Mixed-species RNAseq analysis of human lymphoma cells adhering to mouse stromal cells identifies a core gene set that is also differentially expressed in the lymph node microenvironment of mantle cell lymphoma and chronic lymphocytic leukemia patients
| Autor: | Johan Henriksson, Anthony P. H. Wright, Birgitta Sander, Gustav Arvidsson |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Stromal cell Lymphoma Cell Survival Non-Hodgkin Lymphoma Chronic lymphocytic leukemia Drug Resistance Lymphoma Mantle-Cell Biology Article Cell Line Mice 03 medical and health sciences Cell Line Tumor Paracrine Communication Cell Adhesion medicine Animals Humans Lymph node Sequence Analysis RNA Gene Expression Profiling Hematology medicine.disease Leukemia Lymphocytic Chronic B-Cell Minimal residual disease Coculture Techniques Gene Expression Regulation Neoplastic Leukemia 030104 developmental biology medicine.anatomical_structure Cancer cell Cancer research Mantle cell lymphoma Stromal Cells |
| Zdroj: | Haematologica |
| ISSN: | 1592-8721 0390-6078 |
| Popis: | A subset of hematologic cancer patients is refractory to treatment or suffers relapse, due in part to minimal residual disease, whereby some cancer cells survive treatment. Cell-adhesion-mediated drug resistance is an important mechanism, whereby cancer cells receive survival signals via interaction with e.g. stromal cells. No genome-wide studies of in vitro systems have yet been performed to compare gene expression in different cell subsets within a co-culture and cells grown separately. Using RNA sequencing and species-specific read mapping, we compared transcript levels in human Jeko-1 mantle cell lymphoma cells stably adhered to mouse MS-5 stromal cells or in suspension within a co-culture or cultured separately as well as in stromal cells in co-culture or in separate culture. From 1050 differentially expressed transcripts in adherent mantle cell lymphoma cells, we identified 24 functional categories that together represent four main functional themes, anti-apoptosis, B-cell signaling, cell adhesion/migration and early mitosis. A comparison with previous mantle cell lymphoma and chronic lymphocytic leukemia studies, of gene expression differences between lymph node and blood, identified 116 genes that are differentially expressed in all three studies. From these genes, we suggest a core set of genes (CCL3, CCL4, DUSP4, ETV5, ICAM1, IL15RA, IL21R, IL4I1, MFSD2A, NFKB1, NFKBIE, SEMA7A, TMEM2) characteristic of cells undergoing cell-adhesion-mediated microenvironment signaling in mantle cell lymphoma/chronic lymphocytic leukemia. The model system developed and characterized here together with the core gene set will be useful for future studies of pathways that mediate increased cancer cell survival and drug resistance mechanisms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|