Impact of cell fusion in myeloma marrow microenvironment on tumor progression
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Ziyan Wang1,*, Yuqing Yuan1,*, Liying Zhang1,*, Zhou Min1, Dongming Zhou1, Sun Yu1, Panjun Wang1, Songguang Ju2, Li Jun1 and Jinxiang Fu1
1Hematology Department, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China
2Institute of Biotechnology, Soochow University, Suzhou 215007, PR China
*These authors contributed equaly to this work
Jinxiang Fu, email: [email protected]
Keywords: multiple myeloma; bone marrow microenvironment; mesenchymal stem cell; cell fusion; chemoresistance
Received: December 27, 2017 Accepted: June 05, 2018 Published: July 24, 2018
Background: Mesenchymal stem cells (MSCs) represent a subset of non-hematopoietic adult stem cells, which can also fuse with other cells spontaneously in bone marrow and capable of adopting the phenotype of other cells. The fusion of somatic cells with stem cells can reprogram somatic cells to a pluripotent state. Our research on the fusion of bone marrow mesenchymal stem cells(BM-MSCs) and MM cells demonstrate that the fused cells can exhibit stemness and cancer cell-like characteristics.
Results: We successfully produced a hybrid cells that acquired larger size and multinucleation, in which partial chromatin condensation, a visible nucleolus, and one or more round or oval nucleus. Experiments results showed that the stemness markers highly expressed in these fused cells and there were much more chromosomes in fused cells than those in parental cells as well as exhibited increased resistance to drug treatment.
Conclusions: Our results suggest that cell fusion between BM-MSCs and MM cells could contribute it genomic heterogeneity and play a role on disease progression.
Methods: We fused human BM-MSCs with MM cells lines RPMI 8226 or XG1 in vitro by polyethylene glycol (PEG), and the hybrid cells were sorted by sedimentation assays. The growth, migration, cell cycle, chromosome and drug sensitive of hybrids were assessed by cell counting, cell colony formation, transwell assays, cytogenetic assay and flow cytometry (FCM). The proteins and genes related to stemness and cytokines were tested by western blot and/or real-time quantitative RT-PCR.
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