title: Metastasis initiating cells in primary prostate cancer tissues from transurethral resection of the prostate (TURP) predicts castration-resistant progression and survival of prostate cancer patients.
abstract: BACKGROUND
  We previously reported that the activation of RANK and c-Met signaling components in both experimental mouse models and human prostate cancer (PC) specimens predicts bone metastatic potential and PC patient survival. This study addresses whether a population of metastasis-initiating cells (MICs) known to express a stronger RANKL, phosphorylated c-Met (p-c-Met), and neuropilin-1 (NRP1) signaling network than bystander or dormant cells (BDCs) can be detected in PC tissues from patients subjected to transurethral resection of the prostate (TURP) for urinary obstruction prior to the diagnosis of PC with or without prior hormonal manipulation, and whether the relative abundance of MICs over BDCs could predict castration-resistant progression and PC patient survival.
  
  
  METHODS
  We employed a multiplexed quantum-dot labeling (mQDL) protocol to detect and quantify MICs and BDCs at the single cell level in TURP tissues obtained from 44 PC patients with documented overall survival and castration resistance status.
  
  
  RESULTS
  PC tissues with a higher number of MICs and an activated RANK signaling network, including increased expression of RANKL, p-c-Met, and NRP1 compared to BDCs, were found to correlate with the development of castration resistance and overall survival.
  
  
  CONCLUSIONS
  The assessment of PC cells with MIC and BDC phenotypes in primary PC tissues from hormone-naïve patients can predict the progression to castration resistance and the overall survival of PC patients.
authors.affiliation: Department of Medicine, Uro-Oncology Research Program, Los Angeles, California.
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Biostatistics and Bioinformatics, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Quanlin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Urological Research, Huntington Medical Research Institutes, Huntington Memorial Hospital, Pasadena, California.
authors.forename: Jill
authors.initials: J
authors.lastname: Nuccio
authors.affiliation: Department of Medicine, Uro-Oncology Research Program, Los Angeles, California.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Medicine, Uro-Oncology Research Program, Los Angeles, California.
authors.forename: Peng
authors.initials: P
authors.lastname: Duan
authors.affiliation: Department of Medicine, Uro-Oncology Research Program, Los Angeles, California.
authors.forename: Ruoxiang
authors.initials: R
authors.lastname: Wang
authors.affiliation: Urological Research, Huntington Medical Research Institutes, Huntington Memorial Hospital, Pasadena, California.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Jones
authors.affiliation: Department of Medicine, Uro-Oncology Research Program, Los Angeles, California.|Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
authors.affiliation: Department of Medicine, Uro-Oncology Research Program, Los Angeles, California.
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D045663:Quantum Dots; D053245:RANK Ligand / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015398:Signal Transduction; D015996:Survival Rate; D020728:Transurethral Resection of Prostate / Q000379:methods*
chemical_list: D053245:RANK Ligand; D019859:Proto-Oncogene Proteins c-met; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A
keywords: RANK signaling; dormant cells; metastasis-initiating cells; multiplexed quantum dot labeling; prostate cancer patient survival