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  • Original Paper
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The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor

Abstract

The involvement of Mts1(S100A4), a small Ca2+-binding protein in tumor progression and metastasis had been demonstrated. However, the mechanism by which mts1(S100A4) promoted metastasis had not been identified. Here we demonstrated that Mts1(S100A4) had significant stimulatory effect on the angiogenesis. We detected high incidence of hemangiomas – benign tumors of vascular origin in aged transgenic mice ubiquitously expressing the mts1(S100A4) gene. Furthermore, the serum level of the Mts1(S100A4) protein increased with ageing. Tumors developed in Mts1-transgenic mice revealed an enhanced vascular density. We showed that an oligomeric, but not a dimeric form of the Mts1(S100A4) protein was capable of enhancing the endothelial cell motility in vitro and stimulate the corneal neovascularization in vivo. An oligomeric fraction of the protein was detected in the conditioned media as well as in human serum. The data obtained allowed us to conclude that mts1(S100A4) might induce tumor progression via stimulation of angiogenesis.

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Acknowledgements

We thank IF Larsen, B Kaas, I Skibshøj and D Lützhøft for careful technical assistance. This work was supported by grants from Danish Cancer Society, Danish Medical Research Council, Dansk Kræftforskningsfond, INTAS Programme and the Lundbeck Foundation.

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Correspondence to Noona Ambartsumian.

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Ambartsumian, N., Klingelhöfer, J., Grigorian, M. et al. The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor. Oncogene 20, 4685–4695 (2001). https://doi.org/10.1038/sj.onc.1204636

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