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Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma

Elien De Thaye (UGent) , Koen Van de Vijver (UGent) , Joni Van der Meulen (UGent) , Joachim Taminau (UGent) , Glenn Wagemans (UGent) , Hannelore Denys (UGent) , Jo Van Dorpe (UGent) , Geert Berx (UGent) , Wim Ceelen (UGent) , Jan Van Bocxlaer (UGent) , et al.
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Abstract
Peritoneal spread indicates poor prognosis in patients with serous ovarian carcinoma (SOC) and is generally treated by surgical cytoreduction and chemotherapy. Novel treatment options are urgently needed to improve patient outcome. Clinically relevant cell lines and patient-derived xenograft (PDX) models are of critical importance to therapeutic regimen evaluation. Here, a PDX model was established, by orthotopic engraftment after subperitoneal tumor slurry injection of low-grade SOC, resulting in an early-stage transplantable peritoneal metastasis (PM)-PDX model. Histology confirmed the micropapillary and cribriform growth pattern with intraluminal tumor budding and positivity for PAX8 and WT1. PM-PDX dissociated cells show an epithelial morphotype with a 42 h doubling time and 40% colony forming efficiency, they are low sensitive to platinum derivatives and highly sensitive to paclitaxel (IC50: 6.3 ± 2.2 nM, mean ± SEM). The patient primary tumor, PM, PM-PDX and derived cell line all show a KRAS c.35 G > T (p.(Gly12Val)) mutation and show sensitivity to the MEK inhibitor trametinib in vitro (IC50: 7.2 ± 0.5 nM, mean ± SEM) and in the PM mouse model. These preclinical models closely reflecting patient tumors are useful to further elucidate LGSOC disease progression, therapy response and resistance mechanisms.
Keywords
Multidisciplinary, TUMOR XENOGRAFTS, CANCER, INHIBITOR, MUTATIONS, MODELS, BRAF

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MLA
De Thaye, Elien, et al. “Establishment and Characterization of a Cell Line and Patient-Derived Xenograft (PDX) from Peritoneal Metastasis of Low-Grade Serous Ovarian Carcinoma.” SCIENTIFIC REPORTS, vol. 10, no. 1, 2020, doi:10.1038/s41598-020-63738-6.
APA
De Thaye, E., Van de Vijver, K., Van der Meulen, J., Taminau, J., Wagemans, G., Denys, H., … De Wever, O. (2020). Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma. SCIENTIFIC REPORTS, 10(1). https://doi.org/10.1038/s41598-020-63738-6
Chicago author-date
De Thaye, Elien, Koen Van de Vijver, Joni Van der Meulen, Joachim Taminau, Glenn Wagemans, Hannelore Denys, Jo Van Dorpe, et al. 2020. “Establishment and Characterization of a Cell Line and Patient-Derived Xenograft (PDX) from Peritoneal Metastasis of Low-Grade Serous Ovarian Carcinoma.” SCIENTIFIC REPORTS 10 (1). https://doi.org/10.1038/s41598-020-63738-6.
Chicago author-date (all authors)
De Thaye, Elien, Koen Van de Vijver, Joni Van der Meulen, Joachim Taminau, Glenn Wagemans, Hannelore Denys, Jo Van Dorpe, Geert Berx, Wim Ceelen, Jan Van Bocxlaer, and Olivier De Wever. 2020. “Establishment and Characterization of a Cell Line and Patient-Derived Xenograft (PDX) from Peritoneal Metastasis of Low-Grade Serous Ovarian Carcinoma.” SCIENTIFIC REPORTS 10 (1). doi:10.1038/s41598-020-63738-6.
Vancouver
1.
De Thaye E, Van de Vijver K, Van der Meulen J, Taminau J, Wagemans G, Denys H, et al. Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma. SCIENTIFIC REPORTS. 2020;10(1).
IEEE
[1]
E. De Thaye et al., “Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma,” SCIENTIFIC REPORTS, vol. 10, no. 1, 2020.
@article{8660187,
  abstract     = {{Peritoneal spread indicates poor prognosis in patients with serous ovarian carcinoma (SOC) and is generally treated by surgical cytoreduction and chemotherapy. Novel treatment options are urgently needed to improve patient outcome. Clinically relevant cell lines and patient-derived xenograft (PDX) models are of critical importance to therapeutic regimen evaluation. Here, a PDX model was established, by orthotopic engraftment after subperitoneal tumor slurry injection of low-grade SOC, resulting in an early-stage transplantable peritoneal metastasis (PM)-PDX model. Histology confirmed the micropapillary and cribriform growth pattern with intraluminal tumor budding and positivity for PAX8 and WT1. PM-PDX dissociated cells show an epithelial morphotype with a 42 h doubling time and 40% colony forming efficiency, they are low sensitive to platinum derivatives and highly sensitive to paclitaxel (IC50: 6.3 ± 2.2 nM, mean ± SEM). The patient primary tumor, PM, PM-PDX and derived cell line all show a KRAS c.35 G > T (p.(Gly12Val)) mutation and show sensitivity to the MEK inhibitor trametinib in vitro (IC50: 7.2 ± 0.5 nM, mean ± SEM) and in the PM mouse model. These preclinical models closely reflecting patient tumors are useful to further elucidate LGSOC disease progression, therapy response and resistance mechanisms.}},
  articleno    = {{6688}},
  author       = {{De Thaye, Elien and Van de Vijver, Koen and Van der Meulen, Joni and Taminau, Joachim and Wagemans, Glenn and Denys, Hannelore and Van Dorpe, Jo and Berx, Geert and Ceelen, Wim and Van Bocxlaer, Jan and De Wever, Olivier}},
  issn         = {{2045-2322}},
  journal      = {{SCIENTIFIC REPORTS}},
  keywords     = {{Multidisciplinary,TUMOR XENOGRAFTS,CANCER,INHIBITOR,MUTATIONS,MODELS,BRAF}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{10}},
  title        = {{Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-63738-6}},
  volume       = {{10}},
  year         = {{2020}},
}

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