The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor.
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.
Ambartsumian
N
N
Department of Molecular Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen Ø, Denmark. na@cancer.dk
Klingelhöfer
J
J
Grigorian
M
M
Christensen
C
C
Kriajevska
M
M
Tulchinsky
E
E
Georgiev
G
G
Berezin
V
V
Bock
E
E
Rygaard
J
J
Cao
R
R
Cao
Y
Y
Lukanidin
E
E
D043925:Angiogenesis Inducing Agents / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D019677:Artificial Gene Fusion; D002460:Cell Line; D002465:Cell Movement; D017077:Culture Media, Conditioned / Q000032:analysis; D004730:Endothelium, Vascular / Q000502:physiology; D006391:Hemangioma / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D006903:Hydroxymethylglutaryl CoA Reductases