Circulating tumor cells from prostate cancer patients interact with E-selectin under physiologic blood flow.
Circulating tumor cells from prostate cancer patients interact with E-selectin under physiologic blood flow.
复制标题
DOI：
10.1371/journal.pone.0085143
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nanus DM
中科院分区：
文献类型：
--
作者：
Gakhar G;Navarro VN;Jurish M;Lee GY;Tagawa ST;Akhtar NH;Seandel M;Geng Y;Liu H;Bander NH;Giannakakou P;Christos PJ;King MR;Nanus DM
血源性转移是癌症相关死亡的主要原因，但其机制尚不清楚。血液中的循环肿瘤细胞(CTCs)可能通过不同的途径穿过血管内皮细胞屏障，建立转移的生态位。一些研究表明，在剪切流作用下，前列腺癌(Pca)细胞通过E-选择素/E-选择素配体相互作用在微血管内皮细胞上滚动，理论上促进了细胞外渗，促进了肿瘤转移。然而，目前尚不清楚来自PCa患者的CTCs是否与内皮细胞上表达的E-选择素相互作用，从而启动了肿瘤转移的途径。在此，我们报道了来自PCa患者的CTCs与E-选择素和表达E-选择素的内皮细胞之间存在相互作用。为了检测E-选择素介导的前列腺癌细胞株与转移性前列腺癌患者来源的CTCs的相互作用，我们使用了荧光标记的抗前列腺特异性膜抗原(PSMA)单抗J591-488，该单抗在细胞表面结合后内化。我们使用了由E-选择素包裹的微管和人脐静脉内皮细胞(HUVECs)组成的微型流动装置在平行平板流动室内模拟血管内皮细胞。我们观察到，在剪应力低于3dyn/cm2的情况下，J591-488没有显著改变PCA细胞的滚动行为。31例PCa患者的CTCs显示，CTCs与表达E-选择素和E-选择素的HUVECs在生理剪应力下锚定并稳定地相互作用。有趣的是，在疾病进展期间收集的样本显示CTC/E-选择素的相互作用明显多于在治疗反应期间的样本(p=0.016)。对患者样本唾液酸化路易斯X(sialyl Lewis X，SLeX)表达的分析表明，1.9-18.8%的CTC中高表达SLeX。此外，在抗E-选择素中和抗体的存在下，前列腺CTCs和HUVEC之间的E-选择素介导的相互作用被减弱。CTC与内皮细胞的相互作用为研究前列腺癌CTC作为启动转移途径的潜在黏附机制提供了新的视角。
Hematogenous metastasis accounts for the majority of cancer-related deaths, yet the mechanism remains unclear. Circulating tumor cells (CTCs) in blood may employ different pathways to cross blood endothelial barrier and establish a metastatic niche. Several studies provide evidence that prostate cancer (PCa) cell tethering and rolling on microvascular endothelium via E-selectin/E-selectin ligand interactions under shear flow theoretically promote extravasation and contribute to the development of metastases. However, it is unknown if CTCs from PCa patients interact with E-selectin expressed on endothelium, initiating a route for tumor metastases. Here we report that CTCs derived from PCa patients showed interactions with E-selectin and E-selectin expressing endothelial cells. To examine E-selectin-mediated interactions of PCa cell lines and CTCs derived from metastatic PCa patients, we used fluorescently-labeled anti-prostate specific membrane antigen (PSMA) monoclonal antibody J591-488 which is internalized following cell-surface binding. We employed a microscale flow device consisting of E-selectin-coated microtubes and human umbilical vein endothelial cells (HUVECs) on parallel-plate flow chamber simulating vascular endothelium. We observed that J591-488 did not significantly alter the rolling behavior in PCa cells at shear stresses below 3 dyn/cm2. CTCs obtained from 31 PCa patient samples showed that CTCs tether and stably interact with E-selectin and E-selectin expressing HUVECs at physiological shear stress. Interestingly, samples collected during disease progression demonstrated significantly more CTC/E-selectin interactions than samples during times of therapeutic response (p=0.016). Analysis of the expression of sialyl Lewis X (sLex) in patient samples showed that a small subset comprising 1.9-18.8% of CTCs possess high sLex expression. Furthermore, E-selectin-mediated interactions between prostate CTCs and HUVECs were diminished in the presence of anti-E-selectin neutralizing antibody. CTC-Endothelial interactions provide a novel insight into potential adhesive mechanisms of prostate CTCs as a means to initiate metastasis.
登录
查看更多内容
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
7.4
作者：
Fusi A;Liu Z;Kümmerlen V;Nonnemacher A;Jeske J;Keilholz U
通讯作者：
Keilholz U
影响因子：
11.2
作者：
Dimitroff, CJ;Lechpammer, M;Kutok, JL
通讯作者：
Kutok, JL
影响因子：
3
作者：
Idikio, HA
通讯作者：
Idikio, HA
影响因子：
64.8
作者：
Fuhlbrigge, RC;Kieffer, JD;Kupper, TS
通讯作者：
Kupper, TS