title: Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high-efficiency capture of circulating tumor cells in clear cell renal cell carcinoma patients.
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.
authors: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Shijie
authors: S
authors: Liu
authors: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Zuhong
authors: Z
authors: Tian
authors: Department of Epidemiology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.
authors: Shuang
authors: S
authors: Hou
authors: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Sijun
authors: S
authors: Hu
authors: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Junshen
authors: J
authors: Wu
authors: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Yuming
authors: Y
authors: Jing
authors: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Huimin
authors: H
authors: Sun
authors: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Fei
authors: F
authors: Yu
authors: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors: Libo
authors: L
authors: Zhao
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Ruoxiang
authors: R
authors: Wang
authors: Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California Nanosystems Institute, University of California, Los Angeles, CA 90095, USA.
authors: Hsian-Rong
authors: HR
authors: Tseng
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Haiyen E
authors: HE
authors: Zhau
authors: Uro-Oncology Research Program, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors: Leland W K
authors: LW
authors: Chung
authors: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Kaichun
authors: K
authors: Wu
authors: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Nanotechnology, Beijing 100190, China.
authors: Hao
authors: H
authors: Wang
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99202, USA.
authors: Jason Boyang
authors: JB
authors: Wu
authors: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Yongzhan
authors: Y
authors: Nie
authors: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.|State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Chen
authors: C
authors: Shao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D051926:Basigin / Q000276:immunology / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX / Q000276:immunology / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis*; D002448:Cell Adhesion; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D051926:Basigin; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX
keywords: CD147; carbonic anhydrase 9; circulating tumor cells; renal cell carcinoma