Janker, Lukas and Mayer, Rupert L. and Bileck, Andrea and Kreutz, Dominique and Mader, Johanna C. and Utpatel, Kirsten and Heudobler, Daniel and Agis, Hermine and Gerner, Christopher and Slany, Astrid (2019) Metabolic, Anti-apoptotic and Immune Evasion Strategies of Primary Human Myeloma Cells Indicate Adaptations to Hypoxia. MOLECULAR & CELLULAR PROTEOMICS, 18 (5). pp. 936-953. ISSN 1535-9476, 1535-9484
Full text not available from this repository. (Request a copy)Abstract
Multiple Myeloma (MM) is an incurable plasma cell malignancy primarily localized within the bone marrow (BM). It develops from a premalignant stage, monoclonal gammopathy of undetermined significance (MGUS), often via an intermediate stage, smoldering MM (SMM). The mechanisms of MM progression have not yet been fully understood, all the more because patients with MGUS and SMM already carry similar initial mutations as found in MM cells. Over the last years, increased importance has been attributed to the tumor microenvironment and its role in the pathophysiology of the disease. Adaptations of MM cells to hypoxic conditions in the BM have been shown to contribute significantly to MM progression, independently from the genetic predispositions of the tumor cells. Searching for consequences of hypoxia-induced adaptations in primary human MM cells, CD138-positive plasma cells freshly isolated from BM of patients with different disease stages, comprising MGUS, SMM, and MM, were analyzed by proteome profiling, which resulted in the identification of 6218 proteins. Results have been made fully accessible via ProteomeXchange with identifier PXD010600. Data previously obtained from normal primary B cells were included for comparative purposes. A principle component analysis revealed three clusters, differentiating B cells as well as MM cells corresponding to less and more advanced disease stages. Comparing these three clusters pointed to the alteration of pathways indicating adaptations to hypoxic stress in MM cells on disease progression. Protein regulations indicating immune evasion strategies ofMMcells were determined, supported by immunohistochemical staining, as well as transcription factors involved in MM development and progression. Protein regulatory networks related to metabolic adaptations of the cells became apparent. Results were strengthened by targeted analyses of a selected panel of metabolites in MM cells and MM-associated fibroblasts. Based on our data, new opportunities may arise for developing therapeutic strategies targeting myeloma disease progression. Molecular & Cellular Proteomics 18: 936-953, 2019. DOI:10.1074/mcp.RA119.001390.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOPLASMIC-RETICULUM STRESS; FATTY-ACID SYNTHESIS; MULTIPLE-MYELOMA; BONE-MARROW; ENDOTHELIAL-CELLS; TUMOR-SUPPRESSOR; MITOCHONDRIAL DYSFUNCTION; TRANSCRIPTION FACTOR; HUMAN FIBROBLASTS; INDUCIBLE FACTORS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2020 07:05 |
| Last Modified: | 09 Apr 2020 07:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27088 |
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