title: Ad5/35E1aPSESE4: A novel approach to marking circulating prostate tumor cells with a replication competent adenovirus controlled by PSA/PSMA transcription regulatory elements.
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.
authors.affiliation: Genitourinary Cancer Branch, Research Institute of National Cancer Center, Goyang 410-769, South Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Hwang
authors.affiliation: Genitourinary Cancer Branch, Research Institute of National Cancer Center, Goyang 410-769, South Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Joung
authors.affiliation: Genitourinary Cancer Branch, Research Institute of National Cancer Center, Goyang 410-769, South Korea.
authors.forename: Seung-Phil
authors.initials: SP
authors.lastname: Shin
authors.affiliation: Hematologic Malignancy Branch, Research Institute of National Cancer Center, Goyang 410-769, South Korea.
authors.forename: Moon-Kyung
authors.initials: MK
authors.lastname: Choi
authors.affiliation: Genitourinary Cancer Branch, Research Institute of National Cancer Center, Goyang 410-769, South Korea.
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: New Experimental Therapeutics Branch, Research Institute of National Cancer Center, Goyang 410-769, South Korea.
authors.forename: Yon Hui
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Hematologic Malignancy Branch, Research Institute of National Cancer Center, Goyang 410-769, South Korea.
authors.forename: Weon Seo
authors.initials: WS
authors.lastname: Park
authors.affiliation: Genitourinary Cancer Branch, Research Institute of National Cancer Center, Goyang 410-769, South Korea. Electronic address: leesj@ncc.re.kr.
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Genitourinary Cancer Branch, Research Institute of National Cancer Center, Goyang 410-769, South Korea. Electronic address: uroonco@ncc.re.kr.
authors.forename: Kang Hyun
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; 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 / Q000235:genetics* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D050436:Regulatory Elements, Transcriptional; D015203:Reproducibility of Results; D043823:Taxoids / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D000970:Antineoplastic Agents; D043823:Taxoids; D049452:Green Fluorescent Proteins; D000077143:Docetaxel; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Adenovirus; Circulating tumor cell; Prostate cancer