Research Paper Volume 14, Issue 4 pp 1932—1940
Different tumorigenicity and distinct metastasis and gene signature between orthotopic and subcutaneous neuroblastoma xenografted mice
- 1 Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, China
- 2 National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China
- 3 International Center of Future Science, Jilin University, Changchun, China
Received: December 18, 2021 Accepted: February 15, 2022 Published: February 23, 2022
https://doi.org/10.18632/aging.203913How to Cite
Copyright: © 2022 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Patient-derived (PDX) and cell-derived (CDX) xenograft models are widely used in preclinical studies of human neuroblastoma. In this study, we constructed orthotopic and subcutaneous neuroblastoma CDX models by injecting human neuroblastoma cells into the adrenal gland and the flanks of immunodeficient mice, respectively. The tumorigenesis, metastasis and response to chemotherapy for the two models were also compared. Our results indicated that orthotopic tumor mice showed significantly faster tumor growth than that of subcutaneous mice. Importantly, the expression of PHOX2B and GAB2 was dramatically increased in the tumors of orthotopic CDX mice. Furthermore, orthotopic CDX mice developed multiple organ metastasis resembling that of neuroblastoma patients, while metastasis occurred predominantly in lung in subcutaneous CDX mice. Moreover, the two CDX models showed comparable response to cyclophosphamide treatment. Our results suggest that orthotopic CDX mice are superior to subcutaneous CDX mice as a preclinical model to study human neuroblastoma.