Research Papers:
Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients
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Abstract
Shijie Liu1,2,*, Zuhong Tian2,*, Lei Zhang3,*, Shuang Hou4, Sijun Hu2, Junshen Wu1, Yuming Jing1, Huimin Sun1, Fei Yu1, Libo Zhao5, Ruoxiang Wang6, Hsian-Rong Tseng4, Haiyen E. Zhau6, Leland W.K. Chung6, Kaichun Wu2, Hao Wang7, Jason Boyang Wu8, Yongzhan Nie2, Chen Shao1,2
1Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
2State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
3Department of Epidemiology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China
4Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA
5Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
6Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
7CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Nanotechnology, Beijing 100190, China
8Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99202, USA
*These authors have contributed equally to this work
Correspondence to:
Hao Wang, email: [email protected]
Jason Boyang Wu, email: [email protected]
Yongzhan Nie, email: [email protected]
Chen Shao, email: [email protected]
Keywords: carbonic anhydrase 9, CD147, circulating tumor cells, renal cell carcinoma
Received: January 10, 2016 Accepted: July 18, 2016 Published: August 1, 2016
ABSTRACT
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.
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