title: Ecto-5'-nucleotidase (CD73) is a biomarker for clear cell renal carcinoma stem-like cells.
abstract: Identification of a specific biomarker for cancer stem cells (CSCs) is of potential applications in the development of effective therapeutic strategies for renal cell carcinoma (RCC). In this study, both the RCC cell line 786-O and surgically removed clear cell RCC (ccRCC) tissues were implemented to grew as spheroids in serum-free medium supplemented with mitogens. This subpopulation possessed key characteristics defining CSCs. We also identified that surgically removed ccRCC tissues were heterogenic and there was a subpopulation of cells that was highly stained with rhodamine-123. Based on membrane-proteomic analyses, CD73 was identified as a candidate biomarker. We further found that CD73high cells were highly tumorigenic. As few as 100 CD73high cells were capable of forming xenograft tumors in non obese diabetic/severe combined immunodeficiency disease mice, whereas 1 × 105 CD73low cells did not initiate tumor formation. During successive culture, the CD73high population regenerated both CD73high and CD73low cells, whereas the CD73low population remained low expression level of CD73. Furthermore, the CD73high cells were more resistant to radiation and DNA-damaging agents than the CD73low cells, and expressed a panel of 'stemness' genes at a higher level than the CD73low cells. These findings suggest that a high level of CD73 expression is a bona fide biomarker of ccRCC stem-like cells. Future research will aim at the elucidation of the underlying mechanisms of CD73 in RCC development and the distinct aspects of ccRCC stem-like cells from other tumor types.
authors.affiliation: Medical College, Northwest Minzu University, Lanzhou 730030, China.|Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modem Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Medical College, Henan University, Kaifeng 475001, China.|Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modem Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Urology Surgery, Shuyang Hospital of Traditional Chinese Medicine, Suqian 223600, China.|Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modem Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Institute of Urology, Department of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modem Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modem Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ding
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Hu
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Pei
authors.affiliation: Institute of Urology, Department of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, China.
authors.forename: Zhongjin
authors.initials: Z
authors.lastname: Yue
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhou
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D015720:5'-Nucleotidase
keywords: CD73; SILAC; cancer stem cell; cell surface biomarker; renal cell carcinoma