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

TY - JOUR

T1 - The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor

AU - Ambartsumian, N

AU - Klingelhöfer, Jörg

AU - Grigorian, M

AU - Christensen, C

AU - Kriajevska, M

AU - Tulchinsky, E

AU - Georgiev, G

AU - Berezin, V

AU - Bock, E

AU - Rygaard, J

AU - Cao, R

AU - Cao, Y

AU - Lukanidin, E

PY - 2001/8/2

Y1 - 2001/8/2

N2 - The involvement of Mts1(S100A4), a small Ca(2+)-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.

AB - The involvement of Mts1(S100A4), a small Ca(2+)-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.

KW - Angiogenesis Inducing Agents

KW - Animals

KW - Artificial Gene Fusion

KW - Cell Line

KW - Cell Movement

KW - Culture Media, Conditioned

KW - Endothelium, Vascular

KW - Hemangioma

KW - Hydroxymethylglutaryl CoA Reductases

KW - Mice

KW - Mice, Transgenic

KW - Neovascularization, Pathologic

KW - S100 Proteins

KW - Tumor Cells, Cultured

U2 - 10.1038/sj.onc.1204636

DO - 10.1038/sj.onc.1204636

M3 - Journal article

C2 - 11498791

SN - 0950-9232

VL - 20

SP - 4685

EP - 4695

JO - Oncogene

JF - Oncogene

IS - 34

ER -