Summary
This research project aims to understand how intrinsic and extrinsic factors influence Ewing sarcoma cell fates at metastatic sites, focusing on the role of caveolin-1 and WNT signaling pathways in metastasis patterns of pediatric sarcomas.
Cancer Biology Research Test-Bed Unit 1: Effects of cell-intrinsic and cell-extrinsic signaling and mechanics on metastasis patterns of pediatric sarcomas
US · IL
NIH
grant
awarded
#nih-5U54CA268072-05
What they want
The project will investigate the genesis of metastatic cells from primary tumors and their behavior in the in vivo microenvironment, particularly for Ewing sarcoma. It will leverage zebrafish embryos as a host organism for human tumor xenografts, utilizing multi-modal imaging to identify host tissues associated with metastatic events, define morphologic changes in adapting cells, and probe cancer cell signaling pathways at subcellular resolution. Quantitative imaging, genetic tools, and specific biosensors will be used to study caveolin-1 and WNT-dependent signaling. These studies will be complemented by parallel assays in mouse models and human Ewing sarcoma tumors through collaboration with TDU-2.
Deliverables
- Understanding of effects of microenvironmental interactions on morphology and signaling of metastatic tumor cells
- Assessment of the contribution of Caveolin-1 to metastatic cell adaptation to host environments
- Analysis of the role of WNT signaling in Ewing sarcoma metastasis in genetic models
- Information to inform novel strategies to prevent or ameliorate metastasis in patients with Ewing sarcoma
Technical requirements
- Zebrafish embryo xenograft model for human tumor cells
- Multi-modal imaging techniques
- Genetic tools and specific biosensors
- Quantitative imaging technology (developed by TDU-1)
- Mouse models for parallel assays
- Human Ewing sarcoma tumor samples for parallel assays
