Fischer 344 Rat: A Preclinical Model for Epithelial Ovarian Cancer Folate-Targeted Therapy
Résumé
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
CancerOrigine | Fichiers produits par l'(les) auteur(s) |
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