Establishment and Characterization of Patient-Derived Xenograft Models for Osteosarcoma Lung Metastases

Abstract

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 post-implantation. 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.

Keywords

osteosarcoma / lung metastasis / patient-derived xenograft (PDX) model / subrenal capsule implantation / subcutaneous implantation

Funding

Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission(23141903200)