title: A novel mouse model for multiple myeloma (MOPC315.BM) that allows noninvasive spatiotemporal detection of osteolytic disease.
abstract: 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.
authors.affiliation: Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway.
authors.forename: Peter O
authors.initials: PO
authors.lastname: Hofgaard
authors.forename: Henriette C
authors.initials: HC
authors.lastname: Jodal
authors.forename: Kurt
authors.initials: K
authors.lastname: Bommert
authors.forename: Bertrand
authors.initials: B
authors.lastname: Huard
authors.forename: Jo
authors.initials: J
authors.lastname: Caers
authors.forename: Harald
authors.initials: H
authors.lastname: Carlsen
authors.forename: Rolf
authors.initials: R
authors.lastname: Schwarzer
authors.forename: Nicole
authors.initials: N
authors.lastname: Schünemann
authors.forename: Franziska
authors.initials: F
authors.lastname: Jundt
authors.forename: Mona M
authors.initials: MM
authors.lastname: Lindeberg
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression; D017930:Genes, Reporter; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging; D009101:Multiple Myeloma / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D010014:Osteolysis / Q000000981:diagnostic imaging / Q000473:pathology*; D011859:Radiography; D014162:Transfection