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Exploration of neuroblastoma xenograft models for tumor extracellular RNA profiling in murine blood plasma

Jill Deleu (UGent) , Hanne Van Droogenbroeck (UGent) , Jasper Anckaert (UGent) , Anneleen Decock (UGent) , Jilke De Wilde (UGent) , Kaat Durinck (UGent) , Liselot Mus (UGent) , Justine Nuytens (UGent) , Muhammad Rishfi (UGent) , Kathleen Schoofs (UGent) , et al.
(2023) EXRNA. 5(2).
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Project
Abstract
Background: Minimally invasive liquid biopsies are becoming increasingly important in the diagnosis and treatment follow-up of cancer patients, including children with neuroblastoma. Such biopsies contain various biomarker analytes, including extracellular RNA (exRNA) with the potential to reflect dynamic changes in the tumor. However, it is challenging to distinguish tumor-derived exRNA from normal RNA. To overcome this limitation, xenograft models serve as a practical tool. In a mouse engrafted with human tumor cells, human exRNA is by definition originating from the tumor, whereas murine exRNA is host-derived. To study treatment response by monitoring tumor-derived exRNA, xenograft models with a high release of tumor exRNA into the circulation are desirable. Methods: The aim of this study was to evaluate whether and to what extent the cell line, its engraftment site, or the tumor size influence the amount of tumoral exRNA detected in blood plasma. To that end, four different neuroblastoma cell lines were engrafted in nude mice, either subcutaneously in the flank or orthotopically in the adrenal gland. Tumor sizes were monitored by caliper measurements (subcutaneous grafts) or MRI scans (orthotopic grafts) and blood was collected via terminal cardiac puncture to evaluate the tumoral exRNA fraction. Results: We demonstrate that the tumoral exRNA levels are correlated with the size of the subcutaneous tumor grafts. These levels are also highly dependent on the engrafted cell line. Furthermore, orthotopic engraftment potentially results in superior levels of tumoral exRNA, likely because of higher vascularity of the tumor tissue. Conclusions: Factors as cell line, tumor size and injections site should carefully be considered when performing experiments to study circulating RNA biomarkers.
Keywords
Molecular Biology

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MLA
Deleu, Jill, et al. “Exploration of Neuroblastoma Xenograft Models for Tumor Extracellular RNA Profiling in Murine Blood Plasma.” EXRNA, vol. 5, no. 2, ELS Publishing Co. Limited, 2023, doi:10.55092/exrna20230007.
APA
Deleu, J., Van Droogenbroeck, H., Anckaert, J., Decock, A., De Wilde, J., Durinck, K., … Van Maerken, T. (2023). Exploration of neuroblastoma xenograft models for tumor extracellular RNA profiling in murine blood plasma. EXRNA, 5(2). https://doi.org/10.55092/exrna20230007
Chicago author-date
Deleu, Jill, Hanne Van Droogenbroeck, Jasper Anckaert, Anneleen Decock, Jilke De Wilde, Kaat Durinck, Liselot Mus, et al. 2023. “Exploration of Neuroblastoma Xenograft Models for Tumor Extracellular RNA Profiling in Murine Blood Plasma.” EXRNA 5 (2). https://doi.org/10.55092/exrna20230007.
Chicago author-date (all authors)
Deleu, Jill, Hanne Van Droogenbroeck, Jasper Anckaert, Anneleen Decock, Jilke De Wilde, Kaat Durinck, Liselot Mus, Justine Nuytens, Muhammad Rishfi, Kathleen Schoofs, Franki Speleman, Maaike Van Trimpont, Kimberly Verniers, Nurten Yigit, Jo Vandesompele, Bram De Wilde, and Tom Van Maerken. 2023. “Exploration of Neuroblastoma Xenograft Models for Tumor Extracellular RNA Profiling in Murine Blood Plasma.” EXRNA 5 (2). doi:10.55092/exrna20230007.
Vancouver
1.
Deleu J, Van Droogenbroeck H, Anckaert J, Decock A, De Wilde J, Durinck K, et al. Exploration of neuroblastoma xenograft models for tumor extracellular RNA profiling in murine blood plasma. EXRNA. 2023;5(2).
IEEE
[1]
J. Deleu et al., “Exploration of neuroblastoma xenograft models for tumor extracellular RNA profiling in murine blood plasma,” EXRNA, vol. 5, no. 2, 2023.
@article{01HF4CR7GSX39NBYS2Y2CMQJBK,
  abstract     = {{Background: Minimally invasive liquid biopsies are becoming increasingly important in the diagnosis and treatment follow-up of cancer patients, including children with neuroblastoma. Such biopsies contain various biomarker analytes, including extracellular RNA (exRNA) with the potential to reflect dynamic changes in the tumor. However, it is challenging to distinguish tumor-derived exRNA from normal RNA. To overcome this limitation, xenograft models serve as a practical tool. In a mouse engrafted with human tumor cells, human exRNA is by definition originating from the tumor, whereas murine exRNA is host-derived. To study treatment response by monitoring tumor-derived exRNA, xenograft models with a high release of tumor exRNA into the circulation are desirable. Methods: The aim of this study was to evaluate whether and to what extent the cell line, its engraftment site, or the tumor size influence the amount of tumoral exRNA detected in blood plasma. To that end, four different neuroblastoma cell lines were engrafted in nude mice, either subcutaneously in the flank or orthotopically in the adrenal gland. Tumor sizes were monitored by caliper measurements (subcutaneous grafts) or MRI scans (orthotopic grafts) and blood was collected via terminal cardiac puncture to evaluate the tumoral exRNA fraction. Results: We demonstrate that the tumoral exRNA levels are correlated with the size of the subcutaneous tumor grafts. These levels are also highly dependent on the engrafted cell line. Furthermore, orthotopic engraftment potentially results in superior levels of tumoral exRNA, likely because of higher vascularity of the tumor tissue. Conclusions: Factors as cell line, tumor size and injections site should carefully be considered when performing experiments to study circulating RNA biomarkers.}},
  articleno    = {{0007}},
  author       = {{Deleu, Jill and Van Droogenbroeck, Hanne and Anckaert, Jasper and Decock, Anneleen and De Wilde, Jilke and Durinck, Kaat and Mus, Liselot and Nuytens, Justine and Rishfi, Muhammad and Schoofs, Kathleen and Speleman, Franki and Van Trimpont, Maaike and Verniers, Kimberly and Yigit, Nurten and Vandesompele, Jo and De Wilde, Bram and Van Maerken, Tom}},
  issn         = {{3005-5431}},
  journal      = {{EXRNA}},
  keywords     = {{Molecular Biology}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{19}},
  publisher    = {{ELS Publishing Co. Limited}},
  title        = {{Exploration of neuroblastoma xenograft models for tumor extracellular RNA profiling in murine blood plasma}},
  url          = {{http://doi.org/10.55092/exrna20230007}},
  volume       = {{5}},
  year         = {{2023}},
}

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