Related Experiment Video
Updated: May 25, 2026
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
An osteosarcoma zebrafish model implicates Mmp-19 and Ets-1 as well as reduced host immune response in angiogenesis
Alexander B Mohseny1, Wei Xiao, Ralph Carvalho
1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract:
About 40% of osteosarcoma patients die of metastases. Novel strategies to improve treatment of metastatic patients require a better understanding of the processes involved, like angiogenesis, migration, and the immune response. However, the rarity of osteosarcoma and its heterogeneity make this neoplasm difficult to study. Recently we reported malignant transformation of mouse mesenchymal stem cells (MSCs) which formed osteosarcoma upon transplantation into mice. Here we studied these cells in zebrafish embryos and found that transformed MSCs induced angiogenesis and migrated through the bodies of the embryos, but this was never observed with non-transformed normal MSCs (progenitors of the transformed MSCs). Whole genome expression analysis of both the cells and the host showed that angiogenesis and migration-related genes matrix metalloproteinase 19 (Mmp-19) and erythroblastosis virus E26 oncogene homologue 1 (Ets-1) were overexpressed in transformed MSCs compared to normal MSCs. Investigating the host response, embryos injected with transformed MSCs showed decreased expression of immune response-related genes, especially major histocompatibility complex class 1 (mhc1ze), as compared to embryos injected with normal MSCs. These findings contribute to the identification of genetic events involved in angiogenesis, migration, and host response providing targets as well as an appropriate model for high-throughput drug screens.
Insights
Transformed mouse mesenchymal stem cells (MSCs) promote angiogenesis and migration in zebrafish, while suppressing immune responses. This study identifies key genes like Mmp-19 and Ets-1, offering new therapeutic targets for osteosarcoma metastasis.
Area of Science:
- Oncology
- Developmental Biology
- Genetics
Background:
- Osteosarcoma metastasis is a major cause of patient mortality, necessitating research into underlying mechanisms like angiogenesis, migration, and immune evasion.
- Studying osteosarcoma is challenging due to its rarity and cellular heterogeneity.
- Previous work established a model of mouse mesenchymal stem cells (MSCs) that form osteosarcoma upon transplantation.
Purpose of the Study:
- To investigate the in vivo behavior of transformed MSCs in a zebrafish embryo model.
- To identify genetic factors contributing to osteosarcoma's metastatic potential, including angiogenesis, migration, and host immune response.
- To establish a model for high-throughput drug screening against osteosarcoma metastasis.
Main Methods:
- Transformed and normal mouse mesenchymal stem cells (MSCs) were transplanted into zebrafish embryos.
- Zebrafish embryos were analyzed for angiogenesis and cell migration.
- Whole genome expression analysis was performed on both the transplanted cells and host embryos.
Main Results:
- Transformed MSCs induced significant angiogenesis and migration in zebrafish embryos, unlike normal MSCs.
- Overexpression of angiogenesis and migration-related genes, matrix metalloproteinase 19 (Mmp-19) and erythroblastosis virus E26 oncogene homologue 1 (Ets-1), was observed in transformed MSCs.
- Embryos with transformed MSCs showed suppressed expression of immune response genes, notably major histocompatibility complex class 1 (mhc1ze).
Conclusions:
- Transformed MSCs exhibit pro-angiogenic and migratory properties in vivo, mediated by specific gene expression.
- Osteosarcoma metastasis involves the suppression of host immune responses.
- The zebrafish model and identified genes provide valuable insights and targets for osteosarcoma treatment strategies.
