American Association for Cancer Research
ccr-23-0873_table_s3_suppts3.xlsx (66.8 kB)

Table S3 from Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach

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posted on 2024-02-16, 09:40 authored by Courtney R. Schott, Amanda L. Koehne, Leanne C. Sayles, Elizabeth P. Young, Cuyler Luck, Katherine Yu, Alex G. Lee, Marcus R. Breese, Stanley G. Leung, Hang Xu, Avanthi Tayi Shah, Heng-Yi Liu, Aviv Spillinger, Inge H. Behroozfard, Kieren D. Marini, Phuong T. Dinh, María V. Pons Ventura, Emma N. Vanderboon, Florette K. Hazard, Soo-Jin Cho, Raffi S. Avedian, David G. Mohler, Melissa Zimel, Rosanna Wustrack, Christina Curtis, Marina Sirota, E. Alejandro Sweet-Cordero

Copy number and count data for tumor suppressor genes and oncogenes in primary tumors, PDXs, and PDX-derived cell lines


National Cancer Institute (NCI)

United States Department of Health and Human Services

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St. Baldrick's Foundation (SBF)

Rally Foundation (Rally Foundation, Inc.)



Models to study metastatic disease in rare cancers are needed to advance preclinical therapeutics and to gain insight into disease biology. Osteosarcoma is a rare cancer with a complex genomic landscape in which outcomes for patients with metastatic disease are poor. As osteosarcoma genomes are highly heterogeneous, multiple models are needed to fully elucidate key aspects of disease biology and to recapitulate clinically relevant phenotypes. Matched patient samples, patient-derived xenografts (PDX), and PDX-derived cell lines were comprehensively evaluated using whole-genome sequencing and RNA sequencing. The in vivo metastatic phenotype of the PDX-derived cell lines was characterized in both an intravenous and an orthotopic murine model. As a proof-of-concept study, we tested the preclinical effectiveness of a cyclin-dependent kinase inhibitor on the growth of metastatic tumors in an orthotopic amputation model. PDXs and PDX-derived cell lines largely maintained the expression profiles of the patient from which they were derived despite the emergence of whole-genome duplication in a subset of cell lines. The cell lines were heterogeneous in their metastatic capacity, and heterogeneous tissue tropism was observed in both intravenous and orthotopic models. Single-agent dinaciclib was effective at dramatically reducing the metastatic burden. The variation in metastasis predilection sites between osteosarcoma PDX-derived cell lines demonstrates their ability to recapitulate the spectrum of the disease observed in patients. We describe here a panel of new osteosarcoma PDX-derived cell lines that we believe will be of wide use to the osteosarcoma research community.