Ecto-5′-nucleotidase (CD73) is a biomarker for clear cell renal carcinoma stem-like cells
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Lei Song1,5,*, Wenling Ye2,5,*, Yong Cui3,5,*, Jianzhong Lu4,*, Yanan Zhang5, Nan Ding5, Wentao Hu6, Hailong Pei6, Zhongjin Yue4, Guangming Zhou6
1Medical College, Northwest Minzu University, Lanzhou 730030, China
2Medical College, Henan University, Kaifeng 475001, China
3Department of Urology Surgery, Shuyang Hospital of Traditional Chinese Medicine, Suqian 223600, China
4Institute 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
5Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modem Physics, Chinese Academy of Sciences, Lanzhou 730000, China
6School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China
*These authors contributed equally to this work
Guangming Zhou, email: firstname.lastname@example.org
Zhongjin Yue, email: email@example.com
Keywords: renal cell carcinoma, cancer stem cell, SILAC, cell surface biomarker, CD73
Received: August 29, 2016 Accepted: March 17, 2017 Published: March 29, 2017
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.
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