Multiplexed quantum dot labeling of activated c-Met signaling in castration-resistant human prostate cancer.
The potential application of multiplexed quantum dot labeling (MQDL) for cancer detection and prognosis and monitoring therapeutic responses has attracted the interests of bioengineers, pathologists and cancer biologists. Many published studies claim that MQDL is effective for cancer biomarker detection and useful in cancer diagnosis and prognosis, these studies have not been standardized against quantitative biochemical and molecular determinations. In the present study, we used a molecularly characterized human prostate cancer cell model exhibiting activated c-Met signaling with epithelial to mesenchymal transition (EMT) and lethal metastatic progression to bone and soft tissues as the gold standard, and compared the c-Met cell signaling network in this model, in clinical human prostate cancer tissue specimens and in a castration-resistant human prostate cancer xenograft model. We observed c-Met signaling network activation, manifested by increased phosphorylated c-Met in all three. The downstream survival signaling network was mediated by NF-κB and Mcl-1 and EMT was driven by receptor activator of NF-κB ligand (RANKL), at the single cell level in clinical prostate cancer specimens and the xenograft model. Results were confirmed by real-time RT-PCR and western blots in a human prostate cancer cell model. MQDL is a powerful tool for assessing biomarker expression and it offers molecular insights into cancer progression at both the cell and tissue level with high degree of sensitivity.
Uro-Oncology Research Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Peizhen
P
Hu
Gina C-Y
GC
Chu
Guodong
G
Zhu
Hua
H
Yang
Daniel
D
Luthringer
Gail
G
Prins
Fouad
F
Habib
Yuzhuo
Y
Wang
Ruoxiang
R
Wang
Leland W K
LW
Chung
Haiyen E
HE
Zhau
D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D045663:Quantum Dots; D053245:RANK Ligand / Q000235:genetics; D015203:Reproducibility of Results; D015398:Signal Transduction; D013194:Staining and Labeling / Q000379:methods*; D014162:Transfection; D016896:Treatment Outcome
D053245:RANK Ligand; D019859:Proto-Oncogene Proteins c-met