Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy

Henri Azais (1) , Gurvan Queniat (2) , Caroline Bonner (2) , Olivier Kerdraon (3) , Meryem Tardivel (4) , Bertrand Leroux (1) , Céline Frochot (5) , Nacim Betrouni (1) , Pierre Collinet (1) , Serge Mordon (1)

1 ONCO-THAI - Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189
2 EGID - Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508
3 Centre de Biologie Pathologie
4 BICeL - Plateforme BioImaging Center Lille - PLBS
5 LRGP - Laboratoire Réactions et Génie des Procédés

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 [alpha] (FR[alpha]) 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. FR[alpha] expression by NuTu-19 cells was assessed in vitro by immunofluorescence using "Cytospin(R)" protocol. In vitro folate-targeted compound uptake by NuTu-19 cells was evaluated by incubation of FR[alpha]-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 FR[alpha] tissue expression by several organs of the peritoneal cavity was studied by immunohistochemistry. Results: NuTu-19 cells express FR[alpha] which allows intracellular incorporation of folate-targeted compound by endocytosis. FR[alpha] 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.

Domaines: Cancer

Henri Azais, Gurvan Queniat, Caroline Bonner, Olivier Kerdraon, Meryem Tardivel, et al.. Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy. International Journal of Gynecological Cancer, 2015, pp.1/7. ⟨10.1097/IGC.0000000000000497⟩. ⟨hal-01183323⟩