Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients.
Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients.
复制标题
细胞表面碳酸酐酶 9 和 CD147 抗原的组合能够高效捕获透明细胞肾细胞癌患者的循环肿瘤细胞
DOI：
10.18632/oncotarget.10979
复制
发表时间：
2016-09-13
期刊：
影响因子：
--
通讯作者：
Shao C
中科院分区：
文献类型：
--
作者：
Liu S;Tian Z;Zhang L;Hou S;Hu S;Wu J;Jing Y;Sun H;Yu F;Zhao L;Wang R;Tseng HR;Zhau HE;Chung LW;Wu K;Wang H;Wu JB;Nie Y;Shao C
循环肿瘤细胞（CTC）已成为非侵入性癌症检测和预后的有前途的工具。用于捕获CTC的大多数常规方法使用基于EpCAM的富集策略，其在显示低表达或无EpCAM表达的癌症（例如肾细胞癌（RCC））中不起作用。在这项研究中，我们开发了一组新的细胞表面标志物，包括CA 9和CD 147，作为专门为RCC患者设计的替代CTC捕获抗原。我们通过免疫组化分析发现，在RCC患者队列（n=70）中CA 9和CD 147的表达普遍，两种分子的组合覆盖了97.1%的病例。与传统的基于EpCAM的方法相比，NanoVelcro平台与CA 9-/CD 147-捕获抗体组合显示出显著更高的捕获外周血中CTC模拟肾癌细胞和RCC CTC的效率。在单细胞水平上使用免疫荧光细胞学验证，我们能够在我们的CTC捕获系统中按照公认的标准鉴定RCC患者血液中的真正CTC。我们进一步证明了CTC数量以及间充质标志物波形蛋白的CTC表达状态与疾病进展（包括病理特征和临床分期）的显著相关性。这些结果为开发用于捕获CTC的新型有效靶标/方法提供了新的见解，使CTC成为改善RCC中癌症检测、预后和治疗的有价值的工具。
Circulating tumor cells (CTCs) have emerged as promising tools for noninvasive cancer detection and prognosis. Most conventional approaches for capturing CTCs use an EpCAM-based enrichment strategy, which does not work well in cancers that show low or no expression of EpCAM, such as renal cell carcinoma (RCC). In this study, we developed a new set of cell surface markers including CA9 and CD147 as alternative CTC-capture antigens specifically designed for RCC patients. We showed that the expression of both CA9 and CD147 was prevalent in a RCC patient cohort (n=70) by immunohistochemical analysis, with both molecules in combination covering 97.1% of cases. The NanoVelcro platform combined with CA9-/CD147-capture antibodies demonstrated significantly higher efficiency for capturing both CTC-mimicking renal cancer cells and RCC CTCs in peripheral blood, compared to the conventional EpCAM-based method. Using immunofluorescence cytological validation at the single-cell level, we were able to identify bona fide CTCs in RCC patient blood following the well-accepted criteria in our CTC-capture system. We further demonstrated a significant association of CTC numbers as well as the CTC expression status of Vimentin, a mesenchymal marker, with disease progression, including pathologic features and clinical staging. These results provide new insights into developing novel, effective targets/approaches for capturing CTCs, making CTCs a valuable tool for improved cancer detection, prognosis and treatment in RCC.