This study aims to investigate the feasibility and optimization of patient-derived xenograft(PDX)models for osteosarcoma lung metastases by comparing subrenal capsule and subcutaneous implantation methods. Three osteosarcoma lung metastasis samples meeting the inclusion criteria were implanted into NDG mice using both methods. Tumor growth, histological characteristics, immunohistochemical marker expression, and gene expression profiles were analyzed at eight weeks postimplantation. All three samples successfully established PDX models, with subrenal capsule implantation yielding significantly larger tumor volumes in two cases(p < 0. 05). Histopathological and immunohistochemical analyses demonstrated high morphological similarity between the two models, with Ki67, CD99, and PD-L1 expression retained. Transcriptomic sequencing revealed a strong correlation in global gene expression between the two models(R > 0. 8), with osteosarcoma-specific genes displaying similar expression patterns. These findings suggest that subrenal capsule implantation provides a stable and efficient approach for generating PDX models from limited osteosarcoma lung metastasis tissues while maintaining key biological characteristics comparable to those of subcutaneous models.
| [1] |
Jiang Y F, Wang J Z, Sun M X, et al. Multiomics analysis identifies osteosarcoma subtypes with distinct prognosis indicating stratified treatment[J]. Nature Communications, 2022, 13(1): 7207.
|
| [2] |
Taran S J, Taran R, Malipatil N B. Pediatric osteosarcoma: an updated review[J]. Indian Journal of Medical and Paediatric Oncology, 2017, 38(1): 33-43.
|
| [3] |
Ren J, Xu Y F, Kuang T H, et al. Survival analysis of 104 cases of osteosarcoma with lung metastases[J]. Chinese Journal of Oncology, 2017,(4): 263-268. (in Chinese)
|
| [4] |
Patel T D, Grimm S L, Kanchi R S, et al. Identification of an early survival prognostic gene signature for localized osteosarcoma patients[J]. Scientific Reports, 2024, 14(1): 7327.
|
| [5] |
Sayles L C, Breese M R, Koehne A L, et al. Genome-informed targeted therapy for osteosarcoma[J]. Cancer Discovery, 2019, 9(1): 46-63.
|
| [6] |
Shaikh A B, Li F F, Li M, et al. Present advances and future perspectives of molecular targeted therapy for osteosarcoma[J]. International Journal of Molecular Sciences, 2016, 17(4): 506.
|
| [7] |
Schott C R, Koehne A L, Sayles L C, et al. Osteosarcoma PDX-derived cell line models for preclinical drug evaluation demonstrate metastasis inhibition by dinaciclib through a genometargeted approach[J]. Clinical Cancer Research, 2024, 30(4): 849-864.
|
| [8] |
Blanchard Z, Brown E A, Ghazaryan A, et al. PDX models for functional precision oncology and discovery science[J]. Nature Reviews Cancer, 2025, 25(3): 153-166.
|
| [9] |
Sunil H S, O’donnell K A. Capturing heterogeneity in PDX models: representation matters[J]. Nature Communications, 2024, 15(1): 4652.
|
| [10] |
Abdolahi S, Ghazvinian Z, Muhammadnejad S, et al. Patient-derived xenograft(PDX)models, applications and challenges in cancer research[J]. Journal of Translational Medicine, 2022, 20(1): 206.
|
| [11] |
Fuja D G, Rainusso N C, Shuck R L, et al. Transglutaminase-2 promotes metastatic and stemlike phenotypes in osteosarcoma[J]. American Journal of Cancer Research, 2018, 8(9): 1752-1763.
|
| [12] |
Marques Da Costa M E, Marchais A, Gomez-Brouchet A, et al. In-vitro and in-vivo establishment and characterization of bioluminescent orthotopic chemotherapy-resistant human osteosarcoma models in NSG mice[J]. Cancers, 2019, 11(7): 997.
|
| [13] |
Petrescu D I, Yustein J T, Dasgupta A. Preclinical models for the study of pediatric solid tumors: focus on bone sarcomas[J]. Frontiers in Oncology, 2024, 14: 138848.
|
| [14] |
Marques Da Costa M E, Daudigeos-Dubus E, Gomez-Brouchet A, et al. Establishment and characterization of in vivo orthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice[J]. Cancer Medicine, 2018, 7(3): 665-676.
|
| [15] |
Lima A, Maddalo D. SEMMs: somatically engineered mouse models. a new tool for in vivo disease modeling for basic and translational research[J]. Frontiers in Oncology, 2021, 11: 667189.
|
| [16] |
Ney A, Canciani G, Hsuan J J, et al. Modelling pancreatic neuroendocrine cancer: from bench side to clinic[J]. Cancers, 2020, 12(11):3170.
|
| [17] |
Michalski M N, Williams B O. The past, present, and future of genetically engineered mouse models for skeletal biology[J]. Biomolecules, 2023, 13(9): 1311.
|
| [18] |
Zhao N, Liu Y J, Wei Y Z, et al. Optimization of cell lines as tumour models by integrating multi-omics data[J]. Briefings in Bioinformatics, 2017, 18(3): 515-529.
|
| [19] |
Sarin V, Yu K, Ferguson I D, et al. Evaluating the efficacy of multiple myeloma cell lines as models for patient tumors via transcriptomic correlation analysis[J]. Leukemia, 2020, 34(10): 2754-2765.
|
| [20] |
Zhang Q, Zhang Z Q, Liu G D, et al. B7-H3 targeted CAR-T cells show highly efficient antitumor function against osteosarcoma both in vitro and in vivo[J]. BMC Cancer, 2022, 22(1): 1124.
|
| [21] |
Liu Z G, Yin J Q, Zhou Q, et al. Survival after pulmonary metastasectomy for relapsed osteosarcoma[J]. The Journal of Thoracic and Cardiovascular Surgery, 2022, 163(2): 469-479. e8.
|
| [22] |
Kim Y, Shiba-Ishii A, Nakagawa T, et al. Gene expression profiles of the original tumors influence the generation of PDX models of lung squamous cell carcinoma[J]. Laboratory Investigation, 2021, 101(5): 543-553.
|
| [23] |
Rainusso N, Cleveland H, Hernandez J A, et al. Generation of patient-derived tumor xenografts from percutaneous tumor biopsies in children with bone sarcomas[J]. Pediatric Blood & Cancer, 2019, 66(4): e27579.
|
| [24] |
Beck J, Ren L, Huang S, et al. Canine and murine models of osteosarcoma[J]. Veterinary Pathology, 2022, 59(3): 399-414.
|
| [25] |
Landuzzi L, Manara M C, Lollini P-L, et al. Patient derived xenografts for genome-driven therapy of osteosarcoma[J]. Cells, 2021, 10(2): 416.
|
Funding
Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission(23141903200)
PDF
