Related Experiment Video
Updated: Aug 21, 2026
Establishment of Patient-Derived Xenograft Mouse Model with Human Osteosarcoma Tissues
Published on: March 22, 2024
Human osteosarcoma xenografts and their sensitivity to chemotherapy
Skjalg Bruheim1, Oyvind S Bruland, Knut Breistol
1Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, 0310, Norway. skjalg.bruheim@labmed.uio.no
Abstract:
Despite the increased survival rates of osteosarcoma patients attributed to adjuvant chemotherapy, at least one third of the patients still die due to their disease. Further improvements in the management of osteosarcoma may rely on a more individualised treatment strategy, as well as on the introduction of new drugs. To aid in the preclinical evaluation of new candidate substances against osteosarcoma, we have established 11 human osteosarcoma xenograft lines and characterised them with regard to response to five different reference drugs. Doxorubicin, cisplatin methotrexate, ifosfamide and lomustine were effective in 3/11, 3/11, 1/10, 5/11 and 4/11 of the xenografts, respectively. Five xenografts were resistant to all compounds tested. We also assessed the mRNA expression levels of the xenografts for the O(6)-Methylguanine DNA Methyltransferase (MGMT), DNA topoisomerase II- (Topo II)-alpha, Gluthathione-S-transferase (GST)-pi, Multidrug-resistance related protein (MRP) 1 and Multidrug-resistance (MDR) 1 genes. There was an inverse correlation between the transcript levels of GST-pi and doxorubicin growth inhibition (r=-0.66; p<0.05), and between the transcript levels of MGMT and the effect of lomustine (r=-0.72; p<0.01), whereas the expression of MRP1 and cisplatin growth inhibition was positively correlated (r=0.82; p<0.005). This panel of xenografts should constitute a good tool for pharmacological and molecular studies in osteosarcoma.
Insights
This study established human osteosarcoma xenograft models to test chemotherapy drugs. These models showed varied drug responses and identified correlations between gene expression and drug efficacy, aiding new osteosarcoma treatment development.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Osteosarcoma treatment survival rates have improved with chemotherapy, but a third of patients still succumb to the disease.
- Personalized treatment strategies and novel drug development are crucial for further advancements in osteosarcoma management.
Purpose of the Study:
- To establish and characterize human osteosarcoma xenograft models for preclinical evaluation of new drug candidates.
- To assess the response of these xenografts to five reference chemotherapy drugs and investigate correlations with specific gene expression levels.
Main Methods:
- Established 11 human osteosarcoma xenograft lines.
- Characterized xenograft response to doxorubicin, cisplatin, methotrexate, ifosfamide, and lomustine.
- Assessed mRNA expression of O(6)-Methylguanine DNA Methyltransferase (MGMT), DNA topoisomerase II-alpha (Topo II-alpha), Glutathione-S-transferase-pi (GST-pi), Multidrug-resistance related protein 1 (MRP1), and Multidrug-resistance 1 (MDR1).
Main Results:
- Drug efficacy varied across xenografts, with five lines showing resistance to all tested compounds.
- Identified inverse correlations between GST-pi and doxorubicin, and MGMT and lomustine efficacy.
- Found a positive correlation between MRP1 expression and cisplatin efficacy.
Conclusions:
- The developed panel of human osteosarcoma xenografts provides a valuable tool for preclinical pharmacological and molecular studies.
- These models facilitate the evaluation of novel therapeutic agents and the understanding of drug resistance mechanisms in osteosarcoma.
