Genetically modified mouse models to study the role of metastasis-promoting S100A4(mts1) protein in metastatic mammary cancer.
Transgenic and knockout mouse models are extensively used to study the mechanisms of tumour formation. The availability of mouse models to study metastatic spread of tumours is although quite limited. S100A4(mts1), that belongs to the S100 family of Ca-binding proteins, has been shown to function as a metastasis-promoting protein. We generated strains of mice with modified expression of S100A4 in order to understand the mechanism by which S100A4 protein stimulates metastatic spread of the tumour cells. Transgenic mice over-expressing the S100A4 gene in the mammary gland were crossed with GRS/A mice, characterized by a high incidence of spontaneous non-metastatic mammary tumours. The resulting hybrid mice developed metastatic tumours. Transgenic mice with ubiquitous expression of S100A4 developed vascular tumours, hemangiomas and contained enhanced levels of the S100A4 protein in the blood. Based on these observations we demonstrated that extracellular S100A4 functions as an angiogenic factor. Study of tumour development in the S100A4-deficient mouse model demonstrated key role of extracellular S100A4 in stimulation of tumour development and metastasis formation.
Ambartsumian
Noona
N
Department of Molecular Cancer Biology, Institute for Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. na@cancer.dk
Grigorian
Mariam
M
Lukanidin
Eugene
E
D000818:Animals; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse