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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-131117
  • 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 beMultiple 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.show moreshow less

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Metadaten
Author: Peter O. Hofgaard, Henriette C. Jodal, Kurt Bommert, Bertrand Huard, Jo Caers, Harald Carlsen, Rolf Schwarzer, Nicole Schünemann, Franziska Jundt, Mona M. Lindeberg, Bjarne Bogen
URN:urn:nbn:de:bvb:20-opus-131117
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):PLoS One
Year of Completion:2012
Volume:7
Issue:12
Pagenumber:e51892
Source:PLoS One 7(12): e51892. doi:10.1371/journal.pone.0051892
DOI:https://doi.org/10.1371/journal.pone.0051892
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:B cell; C57BL/KALWRIJ mouse; CD4(+) T-cells; bone disease; differentiation; idiotype; plasma cells; resistance; scid mice; tumor specific antigen
Release Date:2016/12/02
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung