PMID- 27764810
OWN - NLM
STAT- MEDLINE
DCOM- 20180208
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 46
DP  - 2016 Nov 15
TI  - Epithelial-to-mesenchymal transition leads to disease-stage differences in 
      circulating tumor cell detection and metastasis in pre-clinical models of 
      prostate cancer.
PG  - 76125-76139
LID - 10.18632/oncotarget.12682 [doi]
AB  - Metastasis is the cause of most prostate cancer (PCa) deaths and has been 
      associated with circulating tumor cells (CTCs). The presence of >/=5 CTCs/7.5mL of 
      blood is a poor prognosis indicator in metastatic PCa when assessed by the 
      CellSearch(R) system, the "gold standard" clinical platform. However, ~35% of 
      metastatic PCa patients assessed by CellSearch(R) have undetectable CTCs. We 
      hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and 
      subsequent loss of necessary CTC detection markers, with important implications 
      for PCa metastasis. Two pre-clinical assays were developed to assess human CTCs 
      in xenograft models; one comparable to CellSearch(R) (EpCAM-based) and one 
      detecting CTCs semi-independent of EMT status via combined staining with 
      EpCAM/HLA (human leukocyte antigen). In vivo differences in CTC generation, 
      kinetics, metastasis and EMT status were determined using 4 PCa models with 
      progressive epithelial (LNCaP, LNCaP-C42B) to mesenchymal (PC-3, PC-3M) 
      phenotypes. Assay validation demonstrated that the CellSearch(R)-based assay failed 
      to detect a significant number (~40-50%) of mesenchymal CTCs. In vivo, PCa with 
      an increasingly mesenchymal phenotype shed greater numbers of CTCs more quickly 
      and with greater metastatic capacity than PCa with an epithelial phenotype. 
      Notably, the CellSearch(R)-based assay captured the majority of CTCs shed during 
      early-stage disease in vivo, and only after establishment of metastases were a 
      significant number of undetectable CTCs present. This study provides important 
      insight into the influence of EMT on CTC generation and subsequent metastasis, 
      and highlights that novel technologies aimed at capturing mesenchymal CTCs may 
      only be useful in the setting of advanced metastatic disease.
FAU - Lowes, Lori E
AU  - Lowes LE
AD  - Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, 
      Western University, London ON, Canada.
FAU - Goodale, David
AU  - Goodale D
AD  - London Regional Cancer Program, London Health Sciences Centre, London ON, Canada.
FAU - Xia, Ying
AU  - Xia Y
AD  - London Regional Cancer Program, London Health Sciences Centre, London ON, Canada.
FAU - Postenka, Carl
AU  - Postenka C
AD  - London Regional Cancer Program, London Health Sciences Centre, London ON, Canada.
FAU - Piaseczny, Matthew M
AU  - Piaseczny MM
AD  - Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, 
      Western University, London ON, Canada.
FAU - Paczkowski, Freeman
AU  - Paczkowski F
AD  - London Regional Cancer Program, London Health Sciences Centre, London ON, Canada.
FAU - Allan, Alison L
AU  - Allan AL
AD  - Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, 
      Western University, London ON, Canada.
AD  - Department of Oncology, Schulich School of Medicine and Dentistry, Western 
      University, London ON, Canada.
AD  - London Regional Cancer Program, London Health Sciences Centre, London ON, Canada.
AD  - Lawson Health Research Institute, London ON, Canada.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Animals
MH  - Biomarkers, Tumor
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - *Epithelial-Mesenchymal Transition
MH  - Heterografts
MH  - Humans
MH  - Male
MH  - Mice
MH  - Neoplasm Grading
MH  - Neoplasm Metastasis
MH  - Neoplasm Staging
MH  - Neoplastic Cells, Circulating/metabolism/*pathology
MH  - Phenotype
MH  - Prostatic Neoplasms/*diagnosis
MH  - Tumor Burden
PMC - PMC5342801
OTO - NOTNLM
OT  - circulating tumor cells
OT  - epithelial-to-mesenchymal transition
OT  - metastasis
OT  - pre-clinical models
OT  - prostate cancer
COIS- CONFLICTS OF INTEREST A.L.A. has been the recipient of investigator-initiated 
      research support from Janssen Diagnostics and Janssen Oncology (Canada) for 
      clinical studies unrelated to the pre-clinical study reported in this manuscript. 
      All other authors have no potential conflicts to declare.
EDAT- 2016/10/21 06:00
MHDA- 2018/02/09 06:00
PMCR- 2016/11/15
CRDT- 2016/10/21 06:00
PHST- 2016/07/14 00:00 [received]
PHST- 2016/09/29 00:00 [accepted]
PHST- 2016/10/21 06:00 [pubmed]
PHST- 2018/02/09 06:00 [medline]
PHST- 2016/10/21 06:00 [entrez]
PHST- 2016/11/15 00:00 [pmc-release]
AID - 12682 [pii]
AID - 10.18632/oncotarget.12682 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Nov 15;7(46):76125-76139. doi: 10.18632/oncotarget.12682.