title: Non-invasive imaging provides spatiotemporal information on disease progression and response to therapy in a murine model of multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma (MM) is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy.
  
  
  METHODS
  A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM) that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI). Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology.
  
  
  RESULTS
  Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase(+) cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase(+) cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells.
  
  
  CONCLUSIONS
  This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This model is highly suitable for monitoring the effects of different treatment regimens.
authors.affiliation: Department of Medicine II, Würzburg University Clinics, Würzburg, Germany.
authors.forename: Simone S
authors.initials: SS
authors.lastname: Riedel
authors.forename: Anja
authors.initials: A
authors.lastname: Mottok
authors.forename: Christian
authors.initials: C
authors.lastname: Brede
authors.forename: Carina A
authors.initials: CA
authors.lastname: Bäuerlein
authors.forename: Ana-Laura
authors.initials: AL
authors.lastname: Jordán Garrote
authors.forename: Miriam
authors.initials: M
authors.lastname: Ritz
authors.forename: Katharina
authors.initials: K
authors.lastname: Mattenheimer
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.forename: Andreas
authors.initials: A
authors.lastname: Beilhack
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008558:Melphalan / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D062211:Spatio-Temporal Analysis; D016896:Treatment Outcome
chemical_list: D008156:Luciferases; D008558:Melphalan