The C-terminal domain of canstatin suppresses in vivo tumor growth associated with proliferation of endothelial cells
The C-terminal domain of canstatin suppresses in vivo tumor growth associated with proliferation of endothelial cells
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DOI：
10.1016/j.bbrc.2004.04.038
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发表时间：
2004-05-28
影响因子：
3.1
通讯作者：
Wang, FY
中科院分区：
文献类型：
--
作者：
He, GA;Luo, JX;Wang, FY
血管生成对于尺寸大于几立方毫米的实体瘤的生长和转移至关重要Canstat是IV型胶原蛋白α 2链的非胶原I（NC I）结构域，此前已证明可以抑制体外内皮细胞的增殖并抑制体内肿瘤生长。我们前期的研究表明canstatin-N是canstatin的N端1-89个氨基酸的片段。在体内抑制新生血管形成，在体外有效地诱导内皮细胞凋亡，并且在体内抑制BALB/c小鼠的肿瘤生长。在本研究中，我们证明canstatin的C-末端157-227个氨基酸片段canstatin-C在体外也特异性地抑制人脐静脉内皮细胞的增殖并诱导凋亡，但诱导凋亡的活性，而接近于全长canstatin。远低于canstatin-N。Canstatin-C还在a.剂量为10 mg/kg/天。这些结果表明，canstatin-C是canstatin的抗血管生成结构域，主要与特异性抑制内皮细胞增殖有关，而canstatin-N具有潜在的内皮细胞凋亡诱导活性。(C)2004爱思唯尔公司All rights reserved.
Angiogenesis is Crucial for the growth and metastasis of solid tumors with sizes larger than a few cubic millimeter Canstatin, the non-collagenous I (NC I) domain of alpha2 chain of type IV collagen, was previously shown to inhibit proliferation of endothelial cells in vitro and Suppress in vivo tumor growth. Our previous Studies showed that canstatin-N, the N-terminal 1-89 amino acid fragment of canstatin. inhibited the neovascularization in vivo, potently induced apoptosis of endothelial cells in vitro, and suppressed in vivo tumor growth in BALB/c mice. In the present study, we demonstrated that canstatin-C, the C-terminal 157-227 amino acid fragment of canstatin, also specifically inhibited in vitro the proliferation of human umbilical vein endothelial cells and induced apoptosis, but the apoptosis-inducing activity, while close to that of the full-length canstatin. was much lower than that of canstatin-N. Canstatin-C also suppressed in Vivo tumor growth in BALB/c mice at a. dosage of 10 mg/kg/day. These results suggest that canstatin-C is an anti-angiogenic domain of canstatin mainly associated with the specific inhibition of proliferation of endothelial cells, whereas canstatin-N with the potential apoptosis-inducing activity on endothelial cells. (C) 2004 Elsevier Inc. All rights reserved.