Discrete microfluidics for the isolation of circulating tumor cell subpopulations targeting fibroblast activation protein alpha and epithelial cell adhesion molecule.

Autor:	Witek MA; Department of Chemistry, The University of Kansas, Lawrence, KS 66047, USA.; Center of Biomodular Multiscale Systems for Precision Medicine, The University of Kansas, Lawrence, KS 66047, USA.; Department of Biomedical Engineering, The University of North Carolina, Chapel Hill, NC 27599, USA., Aufforth RD; Department of Surgery, The University of North Carolina, Chapel Hill, NC 27599, USA., Wang H; Department of Biomedical Engineering, The University of North Carolina, Chapel Hill, NC 27599, USA., Kamande JW; Department of Biomedical Engineering, The University of North Carolina, Chapel Hill, NC 27599, USA., Jackson JM; Department of Chemistry, The University of Kansas, Lawrence, KS 66047, USA.; Center of Biomodular Multiscale Systems for Precision Medicine, The University of Kansas, Lawrence, KS 66047, USA., Pullagurla SR; Department of Chemistry, The University of Kansas, Lawrence, KS 66047, USA.; Center of Biomodular Multiscale Systems for Precision Medicine, The University of Kansas, Lawrence, KS 66047, USA., Hupert ML; Department of Biomedical Engineering, The University of North Carolina, Chapel Hill, NC 27599, USA.; BioFluidica, Inc., c/o Carolina Kick-Start, 321 Bondurant Hall, Chapel Hill NC27599, USA., Usary J; Department of Genetics, The University of North Carolina, Chapel Hill, NC 27599, USA.; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA., Wysham WZ; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA.; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UNC-Chapel Hill, NC 27599, USA., Hilliard D; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA.; Animal Histopathology Core, The University of North Carolina, Chapel Hill, NC 27599, USA., Montgomery S; Animal Histopathology Core, The University of North Carolina, Chapel Hill, NC 27599, USA.; Department of Pathology and Laboratory Medicine, The University of North Carolina, Chapel Hill, NC 27599, USA., Bae-Jump V; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA.; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UNC-Chapel Hill, NC 27599, USA., Carey LA; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA.; Department of Medicine, Division of Hematology and Oncology, The University of North Carolina, Chapel Hill, NC 27599, USA., Gehrig PA; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA.; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UNC-Chapel Hill, NC 27599, USA., Milowsky MI; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA., Perou CM; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA., Soper JT; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA.; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, UNC-Chapel Hill, NC 27599, USA., Whang YE; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA., Yeh JJ; Department of Surgery, The University of North Carolina, Chapel Hill, NC 27599, USA.; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA.; Department of Pharmacology, The University of North Carolina, Chapel Hill, NC 27599, USA., Martin G; Roche, Pleasanton, CA 94588, USA., Soper SA; BioEngineering Program, The University of Kansas, Lawrence, KS 66047, USA.; Department of Mechanical Engineering, The University of Kansas, Lawrence, KS 66047, USA.; Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Jazyk:	angličtina
Zdroj:	NPJ precision oncology [NPJ Precis Oncol] 2017; Vol. 1. Date of Electronic Publication: 2017 Jul 25.
DOI:	10.1038/s41698-017-0028-8
Abstrakt:	Circulating tumor cells consist of phenotypically distinct subpopulations that originate from the tumor microenvironment. We report a circulating tumor cell dual selection assay that uses discrete microfluidics to select circulating tumor cell subpopulations from a single blood sample; circulating tumor cells expressing the established marker epithelial cell adhesion molecule and a new marker, fibroblast activation protein alpha, were evaluated. Both circulating tumor cell subpopulations were detected in metastatic ovarian, colorectal, prostate, breast, and pancreatic cancer patients and 90% of the isolated circulating tumor cells did not co-express both antigens. Clinical sensitivities of 100% showed substantial improvement compared to epithelial cell adhesion molecule selection alone. Owing to high purity (>80%) of the selected circulating tumor cells, molecular analysis of both circulating tumor cell subpopulations was carried out in bulk, including next generation sequencing, mutation analysis, and gene expression. Results suggested fibroblast activation protein alpha and epithelial cell adhesion molecule circulating tumor cells are distinct subpopulations and the use of these in concert can provide information needed to navigate through cancer disease management challenges. Competing Interests: Competing interests: The presented CTC isolation technology is being commercialized by Biofluidica, Inc. S.A.S. and M.L.H. hold equity shares in BioFluidica, Inc. M.A.W. declares conflict of interest as spouse of M.L.H. The remaining authors declare that they have no competing financial interests.
Databáze:	MEDLINE
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