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A Microfluidic Chip Enables Isolation of Exosomes and Establishment of Their Protein Profiles and Associated Signaling Pathways in Ovarian Cancer.
Dorayappan, Kalpana Deepa Priya; Gardner, Miranda L; Hisey, Colin L; Zingarelli, Roman A; Smith, Brentley Q; Lightfoot, Michelle D S; Gogna, Rajan; Flannery, Meghan M; Hays, John; Hansford, Derek J; Freitas, Michael A; Yu, Lianbo; Cohn, David E; Selvendiran, Karuppaiyah.
Afiliação
  • Dorayappan KDP; Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • Gardner ML; Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, Columbus, Ohio.
  • Hisey CL; Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio.
  • Zingarelli RA; Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • Smith BQ; Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • Lightfoot MDS; Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • Gogna R; Champalimaud Center for the Unknown, Lisbon, Portugal.
  • Flannery MM; Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • Hays J; Division of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • Hansford DJ; Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio.
  • Freitas MA; Department of Cancer Biology and Genetics, Comprehensive Cancer Center, The Ohio State University, Wexner Medical Center, Columbus, Ohio.
  • Yu L; Department of Biostatistics, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • Cohn DE; Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • Selvendiran K; Division of Gynecologic Oncology, Department of Obstetrics/Gynecology, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, Ohio. karuppaiyah.1@osu.edu.
Cancer Res ; 79(13): 3503-3513, 2019 07 01.
Article em En | MEDLINE | ID: mdl-31097475
ABSTRACT
Because of limits on specificity and purity to allow for in-depth protein profiling, a standardized method for exosome isolation has yet to be established. In this study, we describe a novel, in-house microfluidic-based device to isolate exosomes from culture media and patient samples. This technology overcomes contamination issues because sample separation is based on the expression of highly specific surface markers CD63 and EpCAM. Mass spectrometry revealed over 25 exosome proteins that are differentially expressed in high-grade serous ovarian cancer (HGSOC) cell lines compared with normal cells-ovarian surface epithelia cells and fallopian tube secretory epithelial cells (FTSEC). Top exosome proteins were identified on the basis of their fold change and statistical significance between groups. Ingenuity pathway analysis identified STAT3 and HGF as top regulator proteins. We further validated exosome proteins of interest (pSTAT3, HGF, and IL6) in HGSOC samples of origin-based cell lines (OVCAR-8, FTSEC) and in early-stage HGSOC patient serum exosome samples using LC/MS-MS and proximity extension assay. Our microfluidic device will allow us to make new discoveries for exosome-based biomarkers for the early detection of HGSOC and will contribute to the development of new targeted therapies based on signaling pathways that are unique to HGSOC, both of which could improve the outcome for women with HGSOC.

SIGNIFICANCE:

A unique platform utilizing a microfluidic device enables the discovery of new exosome-based biomarkers in ovarian cancer.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Biomarcadores Tumorais / Separação Celular / Cistadenocarcinoma Seroso / Microfluídica / Exossomos Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Biomarcadores Tumorais / Separação Celular / Cistadenocarcinoma Seroso / Microfluídica / Exossomos Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article