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

The involvement of Mts1(S100A4), a small Call-binding protein in tumor prog ression and metastasis had been demonstrated. However, the mechanism by whi ch mts1(S100A4) promoted metastasis had not been identified. Here we demons trated that Mts1(S100A4) had significant stimulatory effect on the angiogen esis. We detected high incidence of hemangiomas - benign tumors of vascular origin in aged transgenic mice ubiquitously expressing the mts1(S100A4) ge ne. Furthermore, the serum level of the Mts1(Sl00A4) protein increased with ageing. Tumors developed in Mts1-transgenic mice revealed an enhanced vasc ular density. We showed that an oligomeric, but not a dimeric form of the M ts1(S100A4) protein was capable of enhancing the endothelial cell motility in vitro and stimulate the corneal neovascularization in vivo. An oligomeri c 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.