The 5TMM series: a useful in vivo mouse model of human multiple myeloma

Asosingh, Kewal; Rádl, J.; Riet, Van; B, Van Camp; Vanderkerken, Karin

doi:10.1038/sj.thj.6200052

Cited by 121 publications

(108 citation statements)

References 27 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…We can assume that when IGF-1 stimulates VEGF secretion by the MM cells in the BM, this will induce endothelial cell growth and vascularisation. As we have already shown that the IGF-1R expression on MM cells is upregulated after contact of the MM cells with BM endothelial cells (Asosingh et al, 2000b), this enhanced vascularisation will increase the effect of IGF-1 even further creating a repeating circle. Moreover, BM endothelial cells can also support the proliferation of MM cells in a way similar to fibroblasts (Szelenyi et al, 2002).…”

Section: Discussionmentioning

confidence: 91%

“…Our group has already described the chemotactic effect of IGF-1 on the 5TMM cells (Vanderkerken et al, 1999;Asosingh et al, 2000b). We have previously shown that F-actin assembly correlates with MM cell migration (Menu et al, 2002).…”

Section: Signal Transduction In F-actin Assemblymentioning

confidence: 89%

“…We have already shown by FACS analysis that the 5T33MM cells express the IGF-1R (Asosingh et al, 2000b). As a first step in defining the IGF-1 signalling pathways, the phosphorylation by IGF-1 of the MAP kinases ERK1/2, p38 and JNK was determined.…”

Section: Activation Of Signal Transduction Elements In Response To Igmentioning

confidence: 99%

See 2 more Smart Citations

Specific roles for the PI3K and the MEK–ERK pathway in IGF-1-stimulated chemotaxis, VEGF secretion and proliferation of multiple myeloma cells: study in the 5T33MM model

Kooijman

Valckenborgh

et al. 2004

Br J Cancer

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 91%

Section: Signal Transduction In F-actin Assemblymentioning

confidence: 89%

See 1 more Smart Citation

Specific roles for the PI3K and the MEK–ERK pathway in IGF-1-stimulated chemotaxis, VEGF secretion and proliferation of multiple myeloma cells: study in the 5T33MM model

Kooijman

Valckenborgh

et al. 2004

Br J Cancer

View full text Add to dashboard Cite

“…40 On day 0, naive C57BL/KaLwRij mice were intravenously injected with 5 x 10^5 5T33MM cells. Mice were treated from day 7 onwards with DAC (0.2 mg/kg) (intraperitoneal injection, daily) and/or Quis (1.5 mg/kg) (subcutaneous injection, once every other day).…”

Section: Methodsmentioning

confidence: 99%

Epigenetic treatment of multiple myeloma mediates tumor intrinsic and extrinsic immunomodulatory effects

et al. 2018

Self Cite

View full text Add to dashboard Cite

Immune evasion is an important driver of disease progression in the plasma cell malignancy multiple myeloma. Recent work highlights the potential of epigenetic modulating agents as tool to enhance anti-tumor immunity. The immune modulating effects of the combination of a DNA methyltransferase inhibitor and a histone deacetylase inhibitor in multiple myeloma is insufficiently characterized. Therefore, we used the murine immunocompetent 5T33MM model to investigate hallmarks of immunogenic cell death as well as alterations in the immune cell constitution in the bone marrow of diseased mice in response to the DNA methyltransferase inhibitor decitabine and the histone deacetylase inhibitor quisinostat. Vaccination of mice with 5T33 cells treated with epigenetic compounds delayed tumor development upon a subsequent tumor challenge. In vitro, epigenetic treatment induced ecto-calreticulin and CD47, as well as a type I interferon response. Moreover, treated 5T33vt cells triggered dendritic cell maturation. The combination of decitabine and quisinostat in vivo resulted in combinatory anti-myeloma effects. In vivo, epigenetic treatment increased tumoral ecto-calreticulin and decreased CD47 and PD-L1 expression, increased dendritic cell maturation and reduced CD11b positive cells. Moreover, epigenetic treatment induced a temporal increase in presence of CD8-positive and CD4-positive T cells with naive and memory-like phenotypes based on CD62L and CD44 expression levels, and reduced expression of exhaustion markers PD-1 and TIM3. In conclusion, a combination of a DNA methyltransferase inhibitor and a histone deacetylase inhibitor increased the immunogenicity of myeloma cells and altered the immune cell constitution in the bone marrow of myeloma-bearing mice.

show abstract

“…Tumour cells from diseased mice were isolated from the bone marrow and transplanted into young syngeneic recipients by intravenous injection. By this way, several 5TMM models were developed (Radl et al, 1979) with similar characteristics as the human disease: the disease occurs spontaneously at older age, the MM cells are localised in the bone marrow, tumour load can be assessed by paraproteinaemia, osteolytic lesions develop and the molecular mechanisms are like in humans (Vanderkerken et al, 1996;Radl et al, 1988;Asosingh et al, 2000). As previously reported, the 5T2MM model more closely represents human MM, characterized by a moderate progressive course of the disease and induction of osteolytic lesions, while the 5T33MM model represents an aggressive, rapidly progressive variant (Vanderkerken et al, 1997;Radl et al, 1988).…”

mentioning

confidence: 99%

Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo

Valckenborgh¹,

Raeve

Devy

et al. 2002

Br J Cancer

View full text Add to dashboard Cite

Multiple myeloma is a B cell malignancy. Recently, it has been demonstrated that bone marrow samples of patients with multiple myeloma display an enhanced angiogenesis. The mechanisms involved seem to be multiple and complex. We here demonstrate that the murine 5T multiple myeloma models are able to induce angiogenesis in vitro by using a rat aortic ring assay and in vivo by determining the microvessel density. The rat aortic rings cultured in 5T multiple myeloma conditioned medium exhibit a higher number of longer and more branched microvessels than the rings cultured in control medium. In bone marrow samples from 5T multiple myeloma diseased mice, a statistically significant increase of the microvessel density was observed when compared to bone marrow samples from age-matched controls. The angiogenic phenotype of both 5T multiple myeloma cells could be related, at least in part, to their capacity to produce vascular endothelial growth factor. These data clearly demonstrate that the 5T multiple myeloma models are good models to study angiogenesis in multiple myeloma and will allow to unravel the mechanisms of neovascularisation, as well as to test new putative inhibitors of angiogenesis.

show abstract

The 5TMM series: a useful in vivo mouse model of human multiple myeloma

Cited by 121 publications

References 27 publications

Specific roles for the PI3K and the MEK–ERK pathway in IGF-1-stimulated chemotaxis, VEGF secretion and proliferation of multiple myeloma cells: study in the 5T33MM model

Specific roles for the PI3K and the MEK–ERK pathway in IGF-1-stimulated chemotaxis, VEGF secretion and proliferation of multiple myeloma cells: study in the 5T33MM model

Epigenetic treatment of multiple myeloma mediates tumor intrinsic and extrinsic immunomodulatory effects

Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo

Contact Info

Product

Resources

About