Promotion of experimental thrombus formation by the procoagulant activity of breast cancer cells.
Promotion of experimental thrombus formation by the procoagulant activity of breast cancer cells.
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DOI：
10.1088/1478-3975/8/1/015014
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发表时间：
2011-02
期刊：
影响因子：
2
通讯作者：
McCarty OJ
中科院分区：
文献类型：
--
作者：
Berny-Lang MA;Aslan JE;Tormoen GW;Patel IA;Bock PE;Gruber A;McCarty OJ
常规观察肿瘤患者外周血中的肿瘤栓子，提出了关于这些循环肿瘤细胞的临床相关性的问题。血栓形成是癌症的常见临床表现，循环肿瘤细胞可能在此过程中发挥致病作用。已经描述了癌细胞上凝血相关分子的存在，但是循环肿瘤细胞增强或改变凝血的机制仍然不清楚。在这项研究中，我们利用转移性腺癌细胞系MDA-MB-231和非转移性乳腺上皮细胞系MCF-10A的悬浮液作为循环肿瘤细胞的模型，以确定这些血液外来细胞的血栓形成活性。在人血浆中，转移性MDA-MB-231细胞和非转移性MCF-10A细胞均显著增强凝血动力学。MDA-MB-231和MCF-10A细胞对凝血时间的影响是细胞数量依赖性的，并受到组织因子（TF）中和抗体以及活化因子X和凝血酶抑制剂的抑制。使用荧光显微镜，我们发现MDA-MB-231和MCF-10A细胞都支持荧光标记的凝血酶的结合。此外，在压力驱动流动下的血栓形成模型中，MDA-MB-231和MCF-10A细胞显著缩短了闭塞时间。我们的研究结果表明，乳腺上皮细胞在血液中的存在可以刺激凝血因子依赖的方式，这表明，进入循环的肿瘤细胞可能会促进闭塞性血栓在剪切流条件下的形成。
The routine observation of tumor emboli in the peripheral blood of patients with carcinomas raises questions about the clinical relevance of these circulating tumor cells. Thrombosis is a common clinical manifestation of cancer and circulating tumor cells may play a pathogenetic role in this process. The presence of coagulation-associated molecules on cancer cells has been described, but the mechanisms by which circulating tumor cells augment or alter coagulation remains unclear. In this study we utilized suspensions of a metastatic adenocarcinoma cell line, MDA-MB-231, and a non-metastatic breast epithelial cell line, MCF-10A, as models of circulating tumor cells to determine the thromobogenic activity of these blood-foreign cells. In human plasma, both metastatic MDA-MB-231 cells and non-metastatic MCF-10A cells significantly enhanced clotting kinetics. The effect of MDA-MB-231 and MCF-10A cells on clotting times was cell number-dependent and inhibited by a neutralizing antibody to tissue factor (TF) as well as inhibitors of activated factor X and thrombin. Using fluorescence microscopy, we found that both MDA-MB-231 and MCF-10A cells supported the binding of fluorescently-labeled thrombin. Furthermore, in a model of thrombus formation under pressure-driven flow, MDA-MB-231 and MCF-10A cells significantly decreased the time to occlusion. Our findings indicate that the presence of breast epithelial cells in blood can stimulate coagulation in a TF-dependent manner, suggesting that tumor cells that enter the circulation may promote the formation of occlusive thrombi under shear flow conditions.
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凝血酶受体在乳腺癌侵袭性中的作用。
影响因子：
8.8
作者：
Henrikson, KP;Salazar, SL;Fenton, JW;Pentecost, BT
通讯作者：
Pentecost, BT
影响因子：
--
作者：
Heit, JA;Mohr, DN;Melton, LJ
通讯作者：
Melton, LJ
影响因子：
20.3
作者：
Camerer, E;Qazi, AA;Coughlin, SR
通讯作者：
Coughlin, SR
DOI：
10.1111/j.1538-7836.2009.03368.x
发表时间：
2009-07
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Mackman N
通讯作者：
Mackman N
影响因子：
82.9
作者：
Even-Ram, S;Uziely, B;Bar-Shavit, R
通讯作者：
Bar-Shavit, R