Ad5/35E1aPSESE4: A novel approach to marking circulating prostate tumor cells with a replication competent adenovirus controlled by PSA/PSMA transcription regulatory elements

Cancer Lett. 2016 Mar 1;372(1):57-64. doi: 10.1016/j.canlet.2015.12.018. Epub 2015 Dec 23.

Abstract

Circulating tumor cells serve as useful biomarkers with which to identify disease status associated with survival, metastasis and drug sensitivity. Here, we established a novel application for detecting PSA/PSMA-positive prostate cancer cells circulating in peripheral blood employing an adenovirus called Ad5/35E1aPSESE4. Ad5/35E1aPSESE4 utilized PSES, a chimeric enhancer derived from PSA/PSMA promoters that is highly active with and without androgen. A fluorescence signal mediated by GFP expression upon Ad5/35E1aPSESE4 infection was selectively amplified in PSA/PSMA-positive prostate cancer cells in vitro and ex vivo. Furthermore, for the in vivo model, blood drawn from TRAMP was tested for CTCs with Ad5/35E1aPSESE4 infection and was positive for CTCs at week 16. Validation was performed on patient blood at various clinical stages and found out 1-100 CTCs expressing GFP upon Ad5/35E1aPSESE4 infection. Interestingly, CTC from one patient was confirmed to be sensitive to docetaxel chemotherapeutic reagent and to abundantly express metastasis-related genes like MMP9, Cofilin1, and FCER1G through RNA-seq. Our study established that the usage of Ad5/35E1aPSESE4 is effective in marking PSA/PSMA-positive prostate cancer cells in patient blood to improve the efficacy of utilizing CTCs as a biomarker.

Keywords: Adenovirus; Circulating tumor cell; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / metabolism
  • Adult
  • Animals
  • Antigens, Surface / genetics*
  • Antigens, Surface / metabolism
  • Antineoplastic Agents / pharmacology
  • Case-Control Studies
  • Cell Line, Tumor
  • Disease Progression
  • Docetaxel
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Regulation, Viral
  • Genes, Reporter
  • Glutamate Carboxypeptidase II / genetics*
  • Glutamate Carboxypeptidase II / metabolism
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Humans
  • Kallikreins / genetics*
  • Kallikreins / metabolism
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Staging
  • Neoplastic Cells, Circulating* / drug effects
  • Neoplastic Cells, Circulating* / metabolism
  • Neoplastic Cells, Circulating* / pathology
  • Predictive Value of Tests
  • Prostate-Specific Antigen / genetics*
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / virology*
  • Regulatory Elements, Transcriptional*
  • Reproducibility of Results
  • Taxoids / pharmacology
  • Time Factors
  • Transcription, Genetic*
  • Tumor Cells, Cultured
  • Virus Replication
  • Young Adult

Substances

  • Antigens, Surface
  • Antineoplastic Agents
  • Taxoids
  • Green Fluorescent Proteins
  • Docetaxel
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen