title: Three-dimensional modeling of the human fallopian tube fimbriae.
abstract: OBJECTIVE
  Ovarian cancer is the most lethal gynecological malignancy that affects women. Recent data suggests that the disease may originate in the fallopian fimbriae; however, the anatomical origin of ovarian carcinogenesis remains unclear. This is largely driven by our lack of knowledge regarding the structure and function of normal fimbriae and the relative paucity of models that accurately recapitulate the in vivo fallopian tube. Therefore, a human three-dimensional (3D) culture system was developed to examine the role of the fallopian fimbriae in serous tumorigenesis.
  
  
  METHODS
  Alginate matrix was utilized to support human fallopian fimbriae ex vivo. Fimbriae were cultured with factors hypothesized to contribute to carcinogenesis, namely; H2O2 (1mM) a mimetic of oxidative stress, insulin (5μg/ml) to stimulate glycolysis, and estradiol (E2, 10nM) which peaks before ovulation. Cultures were evaluated for changes in proliferation and p53 expression, criteria utilized to identify potential precursor lesions. Further, secretory factors were assessed after treatment with E2 to identify if steroid signaling induces a pro-tumorigenic microenvironment.
  
  
  RESULTS
  3D fimbriae cultures maintained normal tissue architecture up to 7days, retaining both epithelial subtypes. Treatment of cultures with H2O2 or insulin significantly induced proliferation. However, p53 stabilization was unaffected by any particular treatment, although it was induced by ex vivo culturing. Moreover, E2-alone treatment significantly induced its canonical target PR and expression of IL8, a factor linked to poor outcome.
  
  
  CONCLUSIONS
  3D alginate cultures of human fallopian fimbriae provide an important microphysiological model, which can be further utilized to investigate serous tumorigenesis originating from the fallopian tube.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Eddie
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Quartuccio
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60607, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Shepherd
authors.affiliation: Division of Gynecological Oncology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60607, USA.
authors.forename: Rajul
authors.initials: R
authors.lastname: Kothari
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: J Julie
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Woodruff
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA. Electronic address: joannab@uic.edu.
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Burdette
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D004847:Epithelial Cells / Q000473:pathology; D005187:Fallopian Tubes / Q000033:anatomy & histology* / Q000473:pathology; D005260:Female; D006801:Humans; D008953:Models, Anatomic; D010051:Ovarian Neoplasms / Q000473:pathology*; D046509:Tissue Culture Techniques
keywords: fallopian tube; fimbriae; microphysiological modeling