Ribosomal proteins as distinct 'passengers' of microvesicles: new semantics in myeloma and mesenchymal stem cells' communication
| Autor: | Shelly Tartakover-Matalon, Avivit Neumann, Liat Drucker, Metsada Pasmanik-Chor, Michael Lishner, Mahmoud Dabbah, Osnat Jarchowsky-Dolberg, Yaron S. Brin |
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| Rok vydání: | 2021 |
| Předmět: |
Ribosomal Proteins
0301 basic medicine Cell Communication Biology Proteomics 03 medical and health sciences 0302 clinical medicine Eukaryotic translation Cell-Derived Microparticles Ribosomal protein Cell Line Tumor Physiology (medical) Humans Peptide Chain Initiation Translational Cell Proliferation Biochemistry (medical) EIF4E Mesenchymal stem cell Public Health Environmental and Occupational Health Mesenchymal Stem Cells General Medicine Phenotype Microvesicles Cell biology 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Multiple Myeloma |
| Zdroj: | Translational Research. 236:117-132 |
| ISSN: | 1931-5244 |
| DOI: | 10.1016/j.trsl.2021.04.002 |
| Popis: | Aberrant mesenchymal stem cells (MSCs) in multiple myeloma (MM) bone marrows (BM) promote disease progression and drug resistance. Here, we assayed the protein cargo transported from MM-MSCs to MM cells via microvesicles (MVs) with focus on ribosomal proteins (RPs) and assessment of their influence on translation initiation and design of MM phenotype. Proteomics analysis (mass spectrometry) demonstrated increased levels and repertoire of RPs in MM-MSCs MVs compared to normal donors (ND) counterparts (n = 3-8; P = 9.96E - 08). We limited the RPs load in MM-MSCs MVs (starvation, RSK and XPO1 inhibitions), reapplied the modified MVs to MM cell lines (U266, MM1S), and demonstrated that the RPs are essential to the proliferative effect of MM-MSCs MVs on MM cells (n = 3; P0.05). We also observed that inhibition with KPT-185 (XPO1 inhibitor) displayed the most extensive effect on RPs delivery into the MVs (↓80%; P = 3.12E - 05). Using flow cytometry we assessed the expression of select RPs (n = 10) in BM-MSCs cell populations (ND and MM; n ≥ 6 each). This demonstrated a heterogeneous expression of RPs in MM-MSCs with distinct subgroups, a phenomenon absent from ND-MSCs samples. These findings bring to light a new mechanism in which the tumor microenvironment participates in cancer promotion. MVs-mediated horizontal transfer of RPs between niche MSCs and myeloma cells is a systemic way to bestow pro-cancer advantages. This capacity also differentiates normal MSCs from the MM-modified MSCs and may mark their reprogramming. Future studies will be aimed at assessing the clinical and therapeutic potential of the increased RPs levels in MM-MSCs MVs. |
| Databáze: | OpenAIRE |
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