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

The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor
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DOI:
10.1038/sj.onc.1204636
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发表时间:
2001-08-02
期刊:
影响因子:
8
通讯作者:
Lukanidin, E
Lukanidin, E
中科院分区:
医学1区
文献类型:
--
作者:
Ambartsumian, N;Klingelhöfer, J;Lukanidin, E

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Mts 1(S100 A4)是一种小分子的细胞结合蛋白,它参与了肿瘤的发生、发展和转移。然而,mts 1(S100 A4)促进转移的机制尚未确定。本研究证明Mts 1(S100 A4)对血管生成有明显的促进作用。我们检测到血管瘤的高发病率-血管来源的良性肿瘤在老年转基因小鼠普遍表达的MTS 1(S100 A4)基因。此外,血清Mts 1(Sl 00 A4)蛋白水平随着年龄的增长而增加。在Mts 1转基因小鼠中发展的肿瘤揭示了增强的血管密度。我们发现,Mts 1(S100 A4)蛋白的寡聚体,而不是二聚体形式能够增强内皮细胞的运动在体外和刺激角膜新生血管在体内。在条件培养基以及人血清中检测到蛋白质的寡聚部分。所获得的数据使我们能够得出结论,mts 1(S100 A4)可能通过刺激血管生成诱导肿瘤进展。
The involvement of Mts1(S100A4), a small Call-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(Sl00A4) 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.