Title |
Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379
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Published in |
Oncogene, January 2018
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DOI | 10.1038/s41388-017-0116-9 |
Pubmed ID | |
Authors |
K. P. O’Brien, S. Khan, K. E. Gilligan, H. Zafar, P. Lalor, C. Glynn, C. O’Flatharta, H. Ingoldsby, P. Dockery, A. De Bhulbh, J. R. Schweber, K. St John, M. Leahy, J. M. Murphy, W. M. Gallagher, T. O’Brien, M. J. Kerin, R. M. Dwyer |
Abstract |
Adult Mesenchymal Stem Cells (MSCs) have a well-established tumor-homing capacity, highlighting potential as tumor-targeted delivery vehicles. MSCs secrete extracellular vesicle (EV)-encapsulated microRNAs, which play a role in intercellular communication. The aim of this study was to characterize a potential tumor suppressor microRNA, miR-379, and engineer MSCs to secrete EVs enriched with miR-379 for in vivo therapy of breast cancer. miR-379 expression was significantly reduced in lymph node metastases compared to primary tumor tissue from the same patients. A significant reduction in the rate of tumor formation and growth in vivo was observed in T47D breast cancer cells stably expressing miR-379. In more aggressive HER2-amplified HCC-1954 cells, HCC-379 and HCC-NTC tumor growth rate in vivo was similar, but increased tumor necrosis was observed in HCC-379 tumors. In response to elevated miR-379, COX-2 mRNA and protein was also significantly reduced in vitro and in vivo. MSCs were successfully engineered to secrete EVs enriched with miR-379, with the majority found to be of the appropriate size and morphology of exosomal EVs. Administration of MSC-379 or MSC-NTC cells, or EVs derived from either cell population, resulted in no adverse effects in vivo. While MSC-379 cells did not impact tumor growth, systemic administration of cell-free EVs enriched with miR-379 was demonstrated to have a therapeutic effect. The data presented support miR-379 as a potent tumor suppressor in breast cancer, mediated in part through regulation of COX-2. Exploiting the tumor-homing capacity of MSCs while engineering the cells to secrete EVs enriched with miR-379 holds exciting potential as an innovative therapy for metastatic breast cancer. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Ireland | 12 | 41% |
United States | 2 | 7% |
Belgium | 1 | 3% |
Pakistan | 1 | 3% |
Australia | 1 | 3% |
United Kingdom | 1 | 3% |
Malaysia | 1 | 3% |
Spain | 1 | 3% |
Unknown | 9 | 31% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 12 | 41% |
Scientists | 12 | 41% |
Science communicators (journalists, bloggers, editors) | 3 | 10% |
Practitioners (doctors, other healthcare professionals) | 2 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 121 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 21 | 17% |
Student > Master | 20 | 17% |
Student > Bachelor | 14 | 12% |
Researcher | 10 | 8% |
Student > Doctoral Student | 7 | 6% |
Other | 16 | 13% |
Unknown | 33 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 33 | 27% |
Medicine and Dentistry | 14 | 12% |
Agricultural and Biological Sciences | 10 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 7 | 6% |
Immunology and Microbiology | 5 | 4% |
Other | 16 | 13% |
Unknown | 36 | 30% |