Cancer cell-derived von Willebrand factor enhanced metastasis of gastric adenocarcinoma.
Cancer cell-derived von Willebrand factor enhanced metastasis of gastric adenocarcinoma.
复制标题
癌细胞源性血管性血友病因子增强胃腺癌转移
DOI：
10.1038/s41389-017-0023-5
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发表时间：
2018-01-24
期刊：
影响因子：
6.2
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Yang AJ;Wang M;Wang Y;Cai W;Li Q;Zhao TT;Zhang LH;Houck K;Chen X;Jin YL;Mu JY;Dong JF;Li M
有血液转移的患者预后差。已知血小板可协助癌细胞通过内皮细胞迁移，但血小板介导的癌转移的配体仍不明确。血管性血友病因子（vWF）是一种主要的血小板配体，已被广泛用作癌症和相关炎症的生物标志物。然而，其在癌症生长和转移中的功能作用在很大程度上是未知的。在这里，我们报告说，胃癌患者的细胞和细胞从两个完善的胃癌细胞系表达vWF，并分泌到循环中，它迅速成为细胞结合介导癌细胞聚集和血小板和内皮细胞的相互作用。vWF介导的同型和异型细胞-细胞相互作用促进小鼠模型中vWF过表达胃癌BGC 823细胞的肺移植。抗vWF及其血小板受体GP Ibα的抗体可阻断vWF的促转移活性。抑制vWF表达的抑制性siRNA也降低了vWF表达。这些发现表明癌细胞源性vWF在介导胃癌转移中的因果作用，并将vWF确定为新的治疗靶点。
Cancer prognosis is poor for patients with blood-borne metastasis. Platelets are known to assist cancer cells in transmigrating through the endothelium, but ligands for the platelet-mediated cancer metastasis remain poorly defined. von Willebrand factor (vWF) is a major platelet ligand that has been widely used as a biomarker in cancer and associated inflammation. However, its functional role in cancer growth and metastasis is largely unknown. Here we report that gastric cancer cells from patients and cells from two well-established gastric cancer lines express vWF and secrete it into the circulation, upon which it rapidly becomes cell-bound to mediate cancer-cell aggregation and interaction with platelets and endothelial cells. The vWF-mediated homotypic and heterotypic cell–cell interactions promote the pulmonary graft of vWF-overexpressing gastric cancer BGC823 cells in a mouse model. The metastasis-promoting activity of vWF was blocked by antibodies against vWF and its platelet receptor GP Ibα. It was also reduced by an inhibitory siRNA that suppresses vWF expression. These findings demonstrate a causal role of cancer-cell-derived vWF in mediating gastric cancer metastasis and identify vWF as a new therapeutic target.
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影响因子：
3.7
作者：
Kim SH;Lu HF;Alano CC
通讯作者：
Alano CC
影响因子：
4.7
作者：
GADDUCCI, A;BAICCHI, U;FACCHINI, V
通讯作者：
FACCHINI, V
在流动条件下，对内皮细胞上ULVWF弦线形成和伸长的共价调节。
影响因子：
10.4
作者：
Li, Y.;Choi, H.;Zhou, Z.;Nolasco, L.;Pownall, H. J.;Voorberg, J.;Moake, J. L.;Dong, J. -F.
通讯作者：
Dong, J. -F.
DOI：
10.1161/atvbaha.116.307660
发表时间：
2016-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Dhanesha N;Prakash P;Doddapattar P;Khanna I;Pollpeter MJ;Nayak MK;Staber JM;Chauhan AK
通讯作者：
Chauhan AK
DOI：
10.1016/0006-291x(87)91333-7
发表时间：
1987-05-29
影响因子：
3.1
作者：
HONN, KV;STEINERT, BW;SLOANE, BF
通讯作者：
SLOANE, BF