Ad5/35E1aPSESE4: A novel approach to marking circulating prostate tumor cells with a replication competent adenovirus controlled by PSA/PSMA transcription regulatory elements.
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.
['Hwang|Ji-Eun|JE|', 'Joung|Jae Young|JY|', 'Shin|Seung-Phil|SP|', 'Choi|Moon-Kyung|MK|', 'Kim|Jeong Eun|JE|', 'Kim|Yon Hui|YH|', 'Park|Weon Seo|WS|', 'Lee|Sang-Jin|SJ|', 'Lee|Kang Hyun|KH|']
D000256:Adenoviridae D000328:Adult D000818:Animals D000954:Antigens, Surface D000970:Antineoplastic Agents D016022:Case-Control Studies D045744:Cell Line, Tumor D018450:Disease Progression D000077143:Docetaxel D015972:Gene Expression Regulation, Neoplastic D015967:Gene Expression Regulation, Viral D017930:Genes, Reporter D043425:Glutamate Carboxypeptidase II D049452:Green Fluorescent Proteins D006801:Humans D007610:Kallikreins D008297:Male D008807:Mice, Inbred BALB C D008819:Mice, Nude D009367:Neoplasm Staging D009360:Neoplastic Cells, Circulating D011237:Predictive Value of Tests D017430:Prostate-Specific Antigen D011471:Prostatic Neoplasms D050436:Regulatory Elements, Transcriptional D015203:Reproducibility of Results D043823:Taxoids D013997:Time Factors D014158:Transcription, Genetic D014407:Tumor Cells, Cultured D014779:Virus Replication D055815:Young Adult
Adenovirus Circulating tumor cell Prostate cancer