Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation
Multiple Myeloma (MM) is an incurable haematological malignancy caused by uncontrolled growth of plasma cells. MM pathogenesis is attributed to crosstalk between plasma cells and the bone marrow microenvironment, where extracellular vesicles (EVs) play a role. In this study, EVs secreted from a pane...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/5/1011 |
| _version_ | 1797264734233296896 |
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| author | Rebecca Sheridan Kieran Brennan Despina Bazou Peter O’Gorman David Matallanas Margaret M. Mc Gee |
| author_facet | Rebecca Sheridan Kieran Brennan Despina Bazou Peter O’Gorman David Matallanas Margaret M. Mc Gee |
| author_sort | Rebecca Sheridan |
| collection | DOAJ |
| description | Multiple Myeloma (MM) is an incurable haematological malignancy caused by uncontrolled growth of plasma cells. MM pathogenesis is attributed to crosstalk between plasma cells and the bone marrow microenvironment, where extracellular vesicles (EVs) play a role. In this study, EVs secreted from a panel of MM cell lines were isolated from conditioned media by ultracentrifugation and fluorescently stained EVs were co-cultured with THP-1 monocyte cells. MM EVs from three cell lines displayed a differential yet dose-dependent uptake by THP-1 cells, with H929 EVs displaying the greatest EV uptake compared to MM.1s and U266 EVs suggesting that uptake efficiency is dependent on the cell line of origin. Furthermore, MM EVs increased the secretion of MMP-9 and IL-6 from monocytes, with H929 EVs inducing the greatest effect, consistent with the greatest uptake efficiency. Moreover, monocyte-conditioned media collected following H929 EV uptake significantly increased the migration and proliferation of MM cells. Finally, EV proteome analysis revealed differential cargo enrichment that correlates with disease progression including a significant enrichment of spliceosome-related proteins in H929 EVs compared to the U266 and MM.1s EVs. Overall, this study demonstrates that MM-derived EVs modulate monocyte function to promote tumour growth and metastasis and reveals possible molecular mechanisms involved. |
| first_indexed | 2024-04-25T00:33:36Z |
| format | Article |
| id | doaj.art-a900a0f558024418841b09dec86795db |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-25T00:33:36Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a900a0f558024418841b09dec86795db2024-03-12T16:41:12ZengMDPI AGCancers2072-66942024-02-01165101110.3390/cancers16051011Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and ProliferationRebecca Sheridan0Kieran Brennan1Despina Bazou2Peter O’Gorman3David Matallanas4Margaret M. Mc Gee5School of Biomolecular and Biomedical Science, University College Dublin, Belfield, D04 V1W8 Dublin, IrelandSchool of Biomolecular and Biomedical Science, University College Dublin, Belfield, D04 V1W8 Dublin, IrelandDepartment of Haematology, Mater Misericordiae University Hospital, D07 R2WY Dublin, IrelandDepartment of Haematology, Mater Misericordiae University Hospital, D07 R2WY Dublin, IrelandSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, D04 V1W8 Dublin, IrelandSchool of Biomolecular and Biomedical Science, University College Dublin, Belfield, D04 V1W8 Dublin, IrelandMultiple Myeloma (MM) is an incurable haematological malignancy caused by uncontrolled growth of plasma cells. MM pathogenesis is attributed to crosstalk between plasma cells and the bone marrow microenvironment, where extracellular vesicles (EVs) play a role. In this study, EVs secreted from a panel of MM cell lines were isolated from conditioned media by ultracentrifugation and fluorescently stained EVs were co-cultured with THP-1 monocyte cells. MM EVs from three cell lines displayed a differential yet dose-dependent uptake by THP-1 cells, with H929 EVs displaying the greatest EV uptake compared to MM.1s and U266 EVs suggesting that uptake efficiency is dependent on the cell line of origin. Furthermore, MM EVs increased the secretion of MMP-9 and IL-6 from monocytes, with H929 EVs inducing the greatest effect, consistent with the greatest uptake efficiency. Moreover, monocyte-conditioned media collected following H929 EV uptake significantly increased the migration and proliferation of MM cells. Finally, EV proteome analysis revealed differential cargo enrichment that correlates with disease progression including a significant enrichment of spliceosome-related proteins in H929 EVs compared to the U266 and MM.1s EVs. Overall, this study demonstrates that MM-derived EVs modulate monocyte function to promote tumour growth and metastasis and reveals possible molecular mechanisms involved.https://www.mdpi.com/2072-6694/16/5/1011cancerextracellular vesiclesmultiple myelomabone marrow microenvironmentmetastasisspliceosome |
| spellingShingle | Rebecca Sheridan Kieran Brennan Despina Bazou Peter O’Gorman David Matallanas Margaret M. Mc Gee Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation Cancers cancer extracellular vesicles multiple myeloma bone marrow microenvironment metastasis spliceosome |
| title | Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation |
| title_full | Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation |
| title_fullStr | Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation |
| title_full_unstemmed | Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation |
| title_short | Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation |
| title_sort | multiple myeloma derived extracellular vesicle uptake by monocyte cells stimulates il 6 and mmp 9 secretion and promotes cancer cell migration and proliferation |
| topic | cancer extracellular vesicles multiple myeloma bone marrow microenvironment metastasis spliceosome |
| url | https://www.mdpi.com/2072-6694/16/5/1011 |
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