title: CD117⁺ cells in the circulation are predictive of advanced prostate cancer.
abstract: 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.
authors.affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Kerr
authors.affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.|Glickman Urological and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Ranko
authors.initials: R
authors.lastname: Miocinovic
authors.affiliation: Glickman Urological and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Armine K
authors.initials: AK
authors.lastname: Smith
authors.affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Xiaoxia Z
authors.initials: XZ
authors.lastname: West
authors.affiliation: Department of Anatomic Pathology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Watts
authors.affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Amanda W
authors.initials: AW
authors.lastname: Alzayed
authors.affiliation: Glickman Urological and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Klink
authors.affiliation: Glickman Urological and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mir
authors.affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Sturey
authors.affiliation: Glickman Urological and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.|Department of Anatomic Pathology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.|Taussig Cancer Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hansel
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Warren D
authors.initials: WD
authors.lastname: Heston
authors.affiliation: Glickman Urological and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.|Taussig Cancer Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stephenson
authors.affiliation: Glickman Urological and Kidney Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.|Taussig Cancer Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Byzova
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D018450:Disease Progression; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit