title: Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy.
abstract: OBJECTIVE
  Ovarian cancer prognosis remains dire after primary therapy. Recurrence rates are disappointingly high as 60% of women with advanced epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis and residual tumorous cells during surgery is necessary as they are the main predictive factors of recurrences. Folate receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells. Our aim was to determine if the Fischer model described by Rose et al could be used to evaluate folate-targeted therapies in preclinical studies.
  
  
  METHODS
  NuTu-19 epithelial ovarian cancer cell line was used to induce peritoneal carcinomatosis in female Fischer 344 rats. FRα expression by NuTu-19 cells was assessed in vitro by immunofluorescence using "Cytospin®" protocol. In vitro folate-targeted compound uptake by NuTu-19 cells was evaluated by incubation of FRα-positive ovarian cancer cell lines (NuTu-19/SKOV-3/OVCAR-3/IGROV-1) with or without (control) a folate-targeted photosensitizer. Intracellular incorporation was assessed by confocal microscopy. Determination of in vivo FRα tissue expression by several organs of the peritoneal cavity was studied by immunohistochemistry.
  
  
  RESULTS
  NuTu-19 cells express FRα which allows intracellular incorporation of folate-targeted compound by endocytosis. FRα is expressed in tumor tissue, ovary, and liver. Peritoneum, colon, small intestine, and kidney do not express the receptor.
  
  
  CONCLUSIONS
  Female Fischer 344 rat is an inexpensive reproducible and efficient preclinical model to study ovarian peritoneal carcinomatosis folate-targeted therapies.
authors.affiliation: *University of Lille, Inserm, CHU Lille, U1189-ONCO THAI- Image Assisted Laser Therapy for Oncology, F-59000 Lille, France; †Department of Gynecology, University Hospital of Lille, F-59000 Lille, France; ‡European Genomic Institute for Diabetes, FR 3508, University of Lille, F-59000 Lille, France; §Centre de biologie-pathologie, University of Lille, F-59000 Lille, France; ∥Plate-forme d'imagerie cellulaire BICEL-IFR 114, University of Lille, F-59000 Lille, France; and ¶Laboratoire Réactions et Génie des Procédés, UMR 7274 CNRS-University of Lorraine, Nancy, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Azaïs
authors.forename: Gurvan
authors.initials: G
authors.lastname: Queniat
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonner
authors.forename: Olivier
authors.initials: O
authors.lastname: Kerdraon
authors.forename: Meryem
authors.initials: M
authors.lastname: Tardivel
authors.forename: Gulim
authors.initials: G
authors.lastname: Jetpisbayeva
authors.forename: Céline
authors.initials: C
authors.lastname: Frochot
authors.forename: Nacim
authors.initials: N
authors.lastname: Betrouni
authors.forename: Pierre
authors.initials: P
authors.lastname: Collinet
authors.forename: Serge
authors.initials: S
authors.lastname: Mordon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D058975:Folate Receptor 1 / Q000037:antagonists & inhibitors*; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D058975:Folate Receptor 1; D017319:Photosensitizing Agents; D005492:Folic Acid