| Objective: There is a wealth of information exchange between tumor cells and the tumormicroenvironment components including mesenchymal stem cells (MSCs), which plays avery important role in the progression of neoplastic disease. But the exact mechanisms arestill unclear. We investigated the molecular mechanism of transformation of MSCsinduced by K562leukemia cell line derived microvesicle (MVs) to clarify the novlemechanismas of crosstalk between leukemia cells and MSCs, which help to clarifytumor-associated pathological mechanisms and to provide new therapeutic strategies.Methods and materials: MSCs were isolated by novel whole bone marrow adhesion andidentified by phenotype and pluripotent differentiation. MVs were isolated by differentcentrifugation and observed with confocal laser microscopy, flow cytometry and electronmicroscopy. We performed RT-PCR and western-blot to test mRNA and protein levels ofBCR-ABL1in K562-MVs and MSCs, respectively. Confocal laser microscope was used toobserve the interaction of K562-MVs and MSCs, MTT was carried out to evaluateproliferation K562and MSCs, and RT-PCR and Elisa were performed for the secretion ofcytokines by MSCs.Results: We successfully isolated MSCs from bone marrow using a novel whole bonemarrow adhesion assay. Both mRNA and protein of BCR-ABL1were contained inK562-MVs and were able to be horizontal transferred into MSCs possibly by directintegration. MSCs transformed by K562-MVs secreted more TGF-β1, SCF and MMP-9resulting from the exogenous BCR-ABL1fusion gene, and enhanced the proliferation ofK562via increased expression of TGF-β1.Conclusion: K562-MVs could transform MSCs by transferring the fusion oncogeneBCR-ABL1, acting as a novel way of cross-talk between leukemia cells and MSCs.Blocking the release of tumor cell-derived MV or interfering with the transfer of MVscontents may become a new strategy against tumor disease progression. |
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