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A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases

Epithelial ovarian cancer (EOC) is a deadly gynecologic malignancy, but animal models for the study of EOC pathophysiology and drug efficacy are limited. Based on the finding that women with EOC are at risk for metastasis at a trocar site after laparoscopy, we developed a syngeneic murine model of p...

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Autores principales: Wilkinson-Ryan, Ivy, Pham, Melissa M., Sergent, Petra, Tafe, Laura J., Berwin, Brent L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170253/
https://www.ncbi.nlm.nih.gov/pubmed/30268949
http://dx.doi.org/10.1016/j.tranon.2018.08.020
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author Wilkinson-Ryan, Ivy
Pham, Melissa M.
Sergent, Petra
Tafe, Laura J.
Berwin, Brent L.
author_facet Wilkinson-Ryan, Ivy
Pham, Melissa M.
Sergent, Petra
Tafe, Laura J.
Berwin, Brent L.
author_sort Wilkinson-Ryan, Ivy
collection PubMed
description Epithelial ovarian cancer (EOC) is a deadly gynecologic malignancy, but animal models for the study of EOC pathophysiology and drug efficacy are limited. Based on the finding that women with EOC are at risk for metastasis at a trocar site after laparoscopy, we developed a syngeneic murine model of port-site metastasis of EOC. We leveraged the ID8 murine EOC cell line to induce intra-peritoneal tumors in mice. Once durable intraperitoneal tumor was confirmed with bioluminescence imaging, intra-abdominal wall tumors were induced by abdominal wall puncture with a hollow bore needle. This resulted in a robust system in which C57BL/6 mice developed metastatic deposits at a rate of 66.7% ± 10.77; no intra-abdominal wall metastases were seen in control samples (P = .0003, CI 41.16–90.84). Immunodeficient NOD SCID gamma mice developed puncture site metastases in 70% ± 10.0 of mice and also had no metastases documented in control sites (P = .002, CI 42.24–97.76). In addition we were able to demonstrate the presence of immune infiltrates within the metastatic deposits of C57BL/6 mice via IHC. Therefore, in this study we demonstrate the predictable development of invasive abdominal wall metastases in a syngeneic mouse model of EOC. This model enables studies of the metastatic process and provides a novel system in which to test the effect of therapies on a clinically-relevant model in an immune competent mouse.
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spelling pubmed-61702532018-10-10 A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases Wilkinson-Ryan, Ivy Pham, Melissa M. Sergent, Petra Tafe, Laura J. Berwin, Brent L. Transl Oncol Original article Epithelial ovarian cancer (EOC) is a deadly gynecologic malignancy, but animal models for the study of EOC pathophysiology and drug efficacy are limited. Based on the finding that women with EOC are at risk for metastasis at a trocar site after laparoscopy, we developed a syngeneic murine model of port-site metastasis of EOC. We leveraged the ID8 murine EOC cell line to induce intra-peritoneal tumors in mice. Once durable intraperitoneal tumor was confirmed with bioluminescence imaging, intra-abdominal wall tumors were induced by abdominal wall puncture with a hollow bore needle. This resulted in a robust system in which C57BL/6 mice developed metastatic deposits at a rate of 66.7% ± 10.77; no intra-abdominal wall metastases were seen in control samples (P = .0003, CI 41.16–90.84). Immunodeficient NOD SCID gamma mice developed puncture site metastases in 70% ± 10.0 of mice and also had no metastases documented in control sites (P = .002, CI 42.24–97.76). In addition we were able to demonstrate the presence of immune infiltrates within the metastatic deposits of C57BL/6 mice via IHC. Therefore, in this study we demonstrate the predictable development of invasive abdominal wall metastases in a syngeneic mouse model of EOC. This model enables studies of the metastatic process and provides a novel system in which to test the effect of therapies on a clinically-relevant model in an immune competent mouse. Neoplasia Press 2018-09-27 /pmc/articles/PMC6170253/ /pubmed/30268949 http://dx.doi.org/10.1016/j.tranon.2018.08.020 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original article
Wilkinson-Ryan, Ivy
Pham, Melissa M.
Sergent, Petra
Tafe, Laura J.
Berwin, Brent L.
A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases
title A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases
title_full A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases
title_fullStr A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases
title_full_unstemmed A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases
title_short A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases
title_sort syngeneic mouse model of epithelial ovarian cancer port site metastases
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170253/
https://www.ncbi.nlm.nih.gov/pubmed/30268949
http://dx.doi.org/10.1016/j.tranon.2018.08.020
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