title: A Combinatory Strategy for Detection of Live CTCs Using Microfiltration and a New Telomerase-Selective Adenovirus.
abstract: Circulating tumor cells (CTC) have become an important biomarker for early cancer diagnosis, prognosis, and treatment monitoring. Recently, a replication-competent recombinant adenovirus driven by a human telomerase gene (hTERT) promoter was shown to detect live CTCs in blood samples of patients with cancer. Here, we report a new class of adenoviruses containing regulatory elements that repress the hTERT gene in normal cells. Compared with the virus with only the hTERT core promoter, the new viruses showed better selectivity for replication in cancer cells than in normal cells. In particular, Ad5GTSe, containing three extra copies of a repressor element, displayed a superior tropism for cancer cells among leukocytes and was thus selected for CTC detection in blood samples. To further improve the efficiency and specificity of CTC identification, we tested a combinatory strategy of microfiltration enrichment using flexible micro spring arrays and Ad5GTSe imaging. Our experiments showed that this method efficiently detected both cancer cells spiked into healthy blood and potential CTCs in blood samples of patients with breast and pancreatic cancer, demonstrating its potential as a highly sensitive and reliable system for detection and capture of CTCs of different tumor types.
authors.affiliation: College of Life Science, Northwest A&F University, Taicheng Road, Yangling, Shaanxi, China. Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Sijie
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania. Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington.
authors.forename: Bora
authors.initials: B
authors.lastname: Lim
authors.affiliation: College of Life Science, Northwest A&F University, Taicheng Road, Yangling, Shaanxi, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.affiliation: Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: David J
authors.initials: DJ
authors.lastname: Spector
authors.affiliation: Division of Hematology-Oncology, Penn State Hershey Cancer Institute, Hershey, Pennsylvania.
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
authors.affiliation: Micro & Nano Integrated Biosystem Laboratory, Department of Biomedical Engineering and Materials Research Institute, Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Si-Yang
authors.initials: SY
authors.lastname: Zheng
authors.affiliation: Department of C&M Physiology, Penn State College of Medicine, Hershey, Pennsylvania. Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, Washington. jiyue.zhu@wsu.edu.
authors.forename: Jiyue
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D019098:Telomerase / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase