Characterization of a Novel Mouse Model of Multiple Myeloma and Its Use in Preclinical Therapeutic Assessment
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Fryer, R. A., Graham, T. J., Smith, E. M., Walker-Samuel, S., Morgan, G. J., Robinson, S. P., Davies, F. E.
(2013)
Characterization of a Novel Mouse Model of Multiple Myeloma and Its Use in Preclinical Therapeutic Assessment.
PLOS ONE, 8 (2).
ISSN 1932-6203
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Abstract
To aid preclinical development of novel therapeutics for myeloma, an in vivo model which recapitulates the human condition is required. An important feature of such a model is the interaction of myeloma cells with the bone marrow microenvironment, as this interaction modulates tumour activity and protects against drug-induced apoptosis. Therefore NOD/SCID gamma C-null mice were injected intra-tibially with luciferase-tagged myeloma cells. Disease progression was monitored by weekly bioluminescent imaging (BLI) and measurement of paraprotein levels. Results were compared with magnetic resonance imaging (MRI) and histology. Assessment of model suitability for preclinical drug testing was investigated using bortezomib, melphalan and two novel agents. Cells engrafted at week 3, with a significant increase in BLI radiance occurring between weeks 5 and 7. This was accompanied by an increase in paraprotein secretion, MRI-derived tumour volume and CD138 positive cells within the bone marrow. Treatment with known anti-myeloma agents or novel agents significantly attenuated the increase in all disease markers. In addition, intra-tibial implantation of primary patient plasma cells resulted in development of myeloma within bone marrow. In conclusion, using both myeloma cell lines and primary patient cells, we have developed a model which recapitulates human myeloma by ensuring the key interaction of tumour cells with the microenvironment.
| Item Type: | Article |
|---|---|
| Authors (ICR Faculty only): | Davies, Faith and Robinson, Simon |
| All Authors: | Fryer, R. A., Graham, T. J., Smith, E. M., Walker-Samuel, S., Morgan, G. J., Robinson, S. P., Davies, F. E. |
| Additional Information: | ISI Document Delivery No.: 093IT Times Cited: 0 Cited Reference Count: 21 Fryer, Rosemary A. Graham, Timothy J. Smith, Emma M. Walker-Samuel, Simon Morgan, Gareth J. Robinson, Simon P. Davies, Faith E. Cancer Research UK [C20826/A12103]; Myeloma UK and Kay Kendall Leukaemia Fund; Institute of Cancer Research; Cancer Research UK; Engineering and Physical Sciences Research Council Cancer Imaging Centre; Medical Research Council and Department of Health (England) [C1060/A10334]; National Health Service This work was supported by grants from Cancer Research UK (FD is a Cancer Research UK Senior Fellow, grant number: C20826/A12103), Myeloma UK and Kay Kendall Leukaemia Fund. The authors acknowledge the support received for The Institute of Cancer Research, Cancer Research UK, and Engineering and Physical Sciences Research Council Cancer Imaging Centre, in association with the Medical Research Council and Department of Health (England), grant C1060/A10334, and National Health Service funding to the National Institute for Health Research Biomedical Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Public library science San francisco |
| Uncontrolled Keywords: | scid mice cells transplantation plasmacytoma pathogenesis inhibition strategy leukemia clone myc |
| Research teams: | ICR divisions > Radiotherapy and Imaging > Magnetic Resonance Closed research groups > Myeloma Targeted Treatment |
| Depositing User: | Barry Jenkins |
| Date Deposited: | 22 Mar 2013 15:41 |
| Last Modified: | 16 Nov 2015 14:05 |
| URI: | http://publications.icr.ac.uk/id/eprint/12333 |
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