TY  - JOUR
A1  - Wong, David
A1  - Winter, Oliver
A1  - Hartig, Christina
A1  - Siebels, Svenja
A1  - Szyska, Martin
A1  - Tiburzy, Benjamin
A1  - Meng, Lingzhang
A1  - Kulkarni, Upasana
A1  - Fähnrich, Anke
A1  - Bommert, Kurt
A1  - Bargou, Ralf
A1  - Berek, Claudia
A1  - Van, Trung Chu
A1  - Bogen, Bjarne
A1  - Jundt, Franziska
A1  - Manz, Rudolf Armin
T1  - Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches
JF  - PLOS ONE
N2  - Multiple myeloma is a bone marrow plasma cell tumor which is supported by the external growth factors APRIL and IL-6, among others. Recently, we identified eosinophils and megakaryocytes to be functional components of the micro-environmental niches of benign bone marrow plasma cells and to be important local sources of these cytokines. Here, we investigated whether eosinophils and megakaryocytes also support the growth of tumor plasma cells in the MOPC315. BM model for multiple myeloma. As it was shown for benign plasma cells and multiple myeloma cells, IL-6 and APRIL also supported MOPC315. BM cell growth in vitro, IL-5 had no effect. Depletion of eosinophils in vivo by IL-5 blockade led to a reduction of the early myeloma load. Consistent with this, myeloma growth in early stages was retarded in eosinophil-deficient Delta dblGATA-1 mice. Late myeloma stages were unaffected, possibly due to megakaryocytes compensating for the loss of eosinophils, since megakaryocytes were found to be in contact with myeloma cells in vivo and supported myeloma growth in vitro. We conclude that eosinophils and megakaryocytes in the niches for benign bone marrow plasma cells support the growth of malignant plasma cells. Further investigations are required to test whether perturbation of these niches represents a potential strategy for the treatment of multiple myeloma.
KW  - plasma cells
KW  - human multiple-myeloma
KW  - immune response
KW  - receptor expression
KW  - B-cells
KW  - stromal cells
KW  - dexamethasone
KW  - april
KW  - survival
KW  - Interleukin-5
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115269
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Hofgaard, Peter O.
A1  - Jodal, Henriette C.
A1  - Bommert, Kurt
A1  - Huard, Bertrand
A1  - Caers, Jo
A1  - Carlsen, Harald
A1  - Schwarzer, Rolf
A1  - Schünemann, Nicole
A1  - Jundt, Franziska
A1  - Lindeberg, Mona M.
A1  - Bogen, Bjarne
T1  - A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease
JF  - PLoS One
N2  - 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.
KW  - resistance
KW  - CD4(+) T-cells
KW  - tumor specific antigen
KW  - plasma cells
KW  - B cell
KW  - C57BL/KALWRIJ mouse
KW  - bone disease
KW  - scid mice
KW  - idiotype
KW  - differentiation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131117
VL  - 7
IS  - 12
ER  -