Clinical Research Papers:
CD117+ cells in the circulation are predictive of advanced prostate cancer
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Bethany A. Kerr1,*, Ranko Miocinovic1,2,*, Armine K. Smith2, Xiaoxia Z. West1, Katherine E. Watts3, Amanda W. Alzayed1, Joseph C. Klink2, Maria C. Mir2, Tiffany Sturey1, Donna E. Hansel2,3,4, Warren D. Heston5, Andrew J. Stephenson2,4, Eric A. Klein2, Tatiana V. Byzova1,4
1Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
2Glickman Urological and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
3Department of Anatomic Pathology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
4Taussig Cancer Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
5Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
*These authors have contributed equally to this work
Bethany A. Kerr, e-mail: [email protected]
Keywords: CD117/c-kit, CD133, prostate cancer, tumor progression
Received: August 25, 2014 Accepted: November 20, 2014 Published: December 17, 2014
Circulating tumor cells (CTCs) are associated with cancer progression, aggressiveness and metastasis. However, the frequency and predictive value of CTCs in patients remains unknown. If circulating cells are involved in tumor aggressiveness and metastasis, then cell levels should decline upon tumor removal in localized cancer patients, but remain high in metastatic patients. Accordingly, proposed biomarkers CD117/c-kit, CD133, CXCR4/CD184, and CD34-positive cell percentages in the blood of patients undergoing radical prostatectomy for localized cancer were assessed by flow cytometry prior to intervention and 1–3 months postoperatively. Only circulating CD117+ cell percentages decreased after radical prostatectomy, increased with cancer progression and correlated with high PSA values. Notably, postoperative CD117+ levels did not decrease in patients experiencing biochemical recurrence. In a xenograft model, CD117-enriched tumors were more vascularized and aggressive. Thus, CD117 expression on CTCs promotes tumor progression and could be a biomarker for prostate cancer diagnosis, prognosis, and/or response to therapy.
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