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A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease

Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacyt...

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Autores principales: Hofgaard, Peter O., Jodal, Henriette C., Bommert, Kurt, Huard, Bertrand, Caers, Jo, Carlsen, Harald, Schwarzer, Rolf, Schünemann, Nicole, Jundt, Franziska, Lindeberg, Mona M., Bogen, Bjarne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527494/
https://www.ncbi.nlm.nih.gov/pubmed/23284805
http://dx.doi.org/10.1371/journal.pone.0051892
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author Hofgaard, Peter O.
Jodal, Henriette C.
Bommert, Kurt
Huard, Bertrand
Caers, Jo
Carlsen, Harald
Schwarzer, Rolf
Schünemann, Nicole
Jundt, Franziska
Lindeberg, Mona M.
Bogen, Bjarne
author_facet Hofgaard, Peter O.
Jodal, Henriette C.
Bommert, Kurt
Huard, Bertrand
Caers, Jo
Carlsen, Harald
Schwarzer, Rolf
Schünemann, Nicole
Jundt, Franziska
Lindeberg, Mona M.
Bogen, Bjarne
author_sort Hofgaard, Peter O.
collection PubMed
description Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacytomas (MOPC) develop in the peritoneal cavity of oil-injected BALB/c mice. However, MOPC typically grow extramedullary and are considered poor models of human MM. Here we describe an in vivo-selected MOPC315 variant, called MOPC315.BM, which can be maintained in vitro. When injected i.v. into BALB/c mice, MOPC315.BM cells exhibit tropism for bone marrow. As few as 10(4) MOPC315.BM cells injected i.v. induced paraplegia, a sign of spinal cord compression, in all mice within 3–4 weeks. MOPC315.BM cells were stably transfected with either firefly luciferase (MOPC315.BM.Luc) or DsRed (MOPC315.BM.DsRed) for studies using noninvasive imaging. MOPC315.BM.Luc cells were detected in the tibiofemoral region already 1 hour after i.v. injection. Bone foci developed progressively, and as of day 5, MM cells were detected in multiple sites in the axial skeleton. Additionally, the spleen (a hematopoietic organ in the mouse) was invariably affected. Luminescent signals correlated with serum myeloma protein concentration, allowing for easy tracking of tumor load with noninvasive imaging. Affected mice developed osteolytic lesions. The MOPC315.BM model employs a common strain of immunocompetent mice (BALB/c) and replicates many characteristics of human MM. The model should be suitable for studies of bone marrow tropism, development of osteolytic lesions, drug testing, and immunotherapy in MM.
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spelling pubmed-35274942013-01-02 A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease Hofgaard, Peter O. Jodal, Henriette C. Bommert, Kurt Huard, Bertrand Caers, Jo Carlsen, Harald Schwarzer, Rolf Schünemann, Nicole Jundt, Franziska Lindeberg, Mona M. Bogen, Bjarne PLoS One Research Article Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacytomas (MOPC) develop in the peritoneal cavity of oil-injected BALB/c mice. However, MOPC typically grow extramedullary and are considered poor models of human MM. Here we describe an in vivo-selected MOPC315 variant, called MOPC315.BM, which can be maintained in vitro. When injected i.v. into BALB/c mice, MOPC315.BM cells exhibit tropism for bone marrow. As few as 10(4) MOPC315.BM cells injected i.v. induced paraplegia, a sign of spinal cord compression, in all mice within 3–4 weeks. MOPC315.BM cells were stably transfected with either firefly luciferase (MOPC315.BM.Luc) or DsRed (MOPC315.BM.DsRed) for studies using noninvasive imaging. MOPC315.BM.Luc cells were detected in the tibiofemoral region already 1 hour after i.v. injection. Bone foci developed progressively, and as of day 5, MM cells were detected in multiple sites in the axial skeleton. Additionally, the spleen (a hematopoietic organ in the mouse) was invariably affected. Luminescent signals correlated with serum myeloma protein concentration, allowing for easy tracking of tumor load with noninvasive imaging. Affected mice developed osteolytic lesions. The MOPC315.BM model employs a common strain of immunocompetent mice (BALB/c) and replicates many characteristics of human MM. The model should be suitable for studies of bone marrow tropism, development of osteolytic lesions, drug testing, and immunotherapy in MM. Public Library of Science 2012-12-20 /pmc/articles/PMC3527494/ /pubmed/23284805 http://dx.doi.org/10.1371/journal.pone.0051892 Text en © 2012 Hofgaard et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hofgaard, Peter O.
Jodal, Henriette C.
Bommert, Kurt
Huard, Bertrand
Caers, Jo
Carlsen, Harald
Schwarzer, Rolf
Schünemann, Nicole
Jundt, Franziska
Lindeberg, Mona M.
Bogen, Bjarne
A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease
title A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease
title_full A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease
title_fullStr A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease
title_full_unstemmed A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease
title_short A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease
title_sort novel mouse model for multiple myeloma (mopc315.bm) that allows noninvasive spatiotemporal detection of osteolytic disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527494/
https://www.ncbi.nlm.nih.gov/pubmed/23284805
http://dx.doi.org/10.1371/journal.pone.0051892
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