Follow-up of bone lesions in an experimental multiple myeloma mouse model: description of an in vivo technique using radiography dedicated for mammography

Vanderkerken, K; Goes, E; Raeve, Hendrik De; Rádl, J.; Camp, Ben Van

doi:10.1038/bjc.1996.277

Cited by 39 publications

(24 citation statements)

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“…To determine at which level LN-67LR interactions also influence the in vivo homing of MM cells, we used the murine 5T2MM model. This model has been intensively characterised and was found to express very similar pathological and biological features as human MM (Vanderkerken et al, 1996(Vanderkerken et al, , 1997. In a recent study, we could demonstrate that 5T2MM cells in vivo selectively home to BM and liver and not to other organs.…”

Section: Discussionmentioning

confidence: 90%

Laminin-1-induced migration of multiple myeloma cells involves the high-affinity 67 kD laminin receptor

Broek¹,

Vanderkerken²,

Greef³

et al. 2001

Br J Cancer

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SummaryThe 67 kD laminin receptor (67LR) binds laminin-1 (LN), major component of the basement membrane, with high affinity. In this study, we demonstrated that human multiple myeloma cell lines (HMCL) and murine 5T2MM cells express 67LR. CD38 bright+ plasma cells in fresh multiple myeloma (MM) bone marrow (BM) samples showed weaker 67LR expression, but expression increased after direct exposure to a BM endothelial cell line (4LHBMEC). LN stimulated the in vitro migration of 3 HMCL (MM5.1, U266 and MMS.1), primary MM cells and the murine 5T2MM cells. 67LR has been shown to mediate the actions of LN through binding to CDPGYIGSR, a 9 amino acid sequence from the B1 chain of LN. MM cell migration was partially blocked by peptide 11, a synthetic nonapeptide derived from this amino sequence and also by a blocking antiserum against 67LR. Co-injection of peptide 11 with 5T2MM cells in a murine in vivo model of MM resulted in a decreased homing of 5T2MM cells to the BM compartment. In conclusion, LN acts as a chemoattractant for MM cells by interaction with 67LR. This interaction might be important during extravasation of circulating MM cells.

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Section: Discussionmentioning

confidence: 90%

Laminin-1-induced migration of multiple myeloma cells involves the high-affinity 67 kD laminin receptor

Broek¹,

Vanderkerken²,

Greef³

et al. 2001

Br J Cancer

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“…In contrast, the 5T2 MM model more closely resembles the classical presentation of human MM in several aspects: the course of the disease is moderately progressive, the homing is more restricted to the bone marrow, some maturation towards the plasma cell can be observed and the development of osteolysis can consistently be observed during the course of the disease (Radl, 1985;Vanderkerken et al, 1996). Further, the in vitro growth is 'stroma dependent'.…”

Section: Discussionmentioning

confidence: 93%

“…Briefly, mice were anaesthetized and a radiograph of pelvis and hind legs was performed (Vanderkerken et al, 1996). This method allowed the follow-up of bone lesions in the same mouse.…”

Section: Radiographymentioning

confidence: 99%

Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells in the C57BL/KaLwRij mouse

Vanderkerken¹,

Raeve²,

Goes³

et al. 1997

Br J Cancer

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133

142

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Summary The aim of this study was to evaluate the tissue infiltration and phenotypic adhesion profile of 5T2 multiple myeloma (MM) and 5T33 MM cells and to correlate it with that observed in human disease. For each line, 30 mice were intravenously inoculated with myeloma cells and at a clear-cut demonstrable serum paraprotein concentration; mice were sacrificed and a number of organs removed. The haematoxylin-eosin stainings on paraffin sections were complemented with immunohistochemistry using monoclonal antibodies developed against the specific MM idiotype. When analysed over time, 5T2 MM cells could be observed in bone marrow samples from week 9 after transfer of the cells. For the 5T33 MM, a simultaneous infiltration was observed in bone marrow, spleen and liver 2 weeks after inoculation. Osteolytic lesions consistently developed in the 5T2 MM, but this was not consistent for 5T33 MM. PCNA staining showed a higher proliferative index for the 5T33 MM cells. The expression of adhesion molecules was analysed by immunohistochemistry on cytosmears: both 5T2 MM and 5T33 MM cells were LFA-1, CD44, VLA-4 and VLA-5 positive. We conclude that both lines have a phenotypic adhesion profile analogous to that of human MM cells. As the 5T2 MM cells are less aggressive than the 5T33 MM cells, their organ distribution is more restricted to the bone marrow and osteolytic lesions are consistently present, the former cell line induces myeloma development similar to the human disease.Keywords: multiple myeloma; adhesion molecules; organ involvement; 5T2; 5T33 Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells secreting a monoclonal immunoglobulin (Ig). The disease is mainly localized in the bone marrow. In this microenvironment the myeloma plasma cells receive signals necessary for their proliferation, terminal differentiation and for the secretion of osteoclast-activating factors. The osteoclast-activating factors recruit osteoclasts, which induce in situ osteolytic bone lesions (Bataille et al, 1989;Alsina et al, 1996); this is one of the major characteristics of the disease. It has been suggested that both cytokines and adhesion molecules are involved in this complex network of signals (Van Riet and Van Camp, 1993).To elucidate the exact mechanisms described above, an in vivo MM model is necessary. Radl et al (1979) found that 0.5% of ageing C57BL/KaLwRij mice spontanously developed a disease reminiscent of MM. The MM cells isolated from the bone marrow of different mice (5T MM) did not grow in vitro but could be transplanted by intravenous injection into young recipients of the same strain. This transplantable model resembles the human disease in several aspects (Radl et al, 1988): myeloma occurred spontaneously, the frequency of development of the disease is age related, tumour load can be assessed by paraproteinaemia and the (Radl et al, 1988).In order to understand the homing mechanisms of the 5T MM cells to the bone marrow, it was essential to determine accurately the...

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“…into syngeneic C57BL/KaLwRij mice, 5T myeloma tumor cells home almost exclusively to the bone marrow and infrequently to the spleen. Additionally, bone destruction is evident around tumor foci and the lytic lesions can be visualized by plain radiography, with increased osteoclastic activity documented by bone histomorphometry (7,8,13,14). The original Radl myeloma model was established using whole marrow transplants from mice bearing the 5T33 myeloma (6).…”

Section: Resultsmentioning

confidence: 99%

Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging

Oyajobi

Munoz

Käkönen

et al. 2007

Molecular Cancer Therapeutics

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Development of new therapies for myeloma has been hindered by the lack of suitable preclinical animal models of the disease in which widespread tumor foci in the skeleton can be detected reliably. Traditional means of detecting skeletal tumor infiltration such as histopathology are cumbersome and labor-intensive and do not allow temporal monitoring of tumor progression or regression in response to therapy. To resolve this problem, we modified the Radl 5TGM1 model of myeloma bone disease such that fluorescent myeloma tumors can be optically imaged in situ. Here, we show that murine myeloma 5TGM1 tumor cells, engineered to express enhanced green fluorescent protein (eGFP; 5TGM1-eGFP cells), can be imaged in a temporal fashion using a fluorescence illuminator and a charge-coupled device camera in skeletons of live C57BL/ KaLwRij mice. High-resolution, whole-body images of tumor-bearing mice revealed that myeloma cells homed almost exclusively to the skeleton, with multiple focal

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Follow-up of bone lesions in an experimental multiple myeloma mouse model: description of an in vivo technique using radiography dedicated for mammography

Cited by 39 publications

References 2 publications

Laminin-1-induced migration of multiple myeloma cells involves the high-affinity 67 kD laminin receptor

Laminin-1-induced migration of multiple myeloma cells involves the high-affinity 67 kD laminin receptor

Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells in the C57BL/KaLwRij mouse

Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging

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