Related Experiment Video
Updated: May 13, 2025
Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy
Published on: September 16, 2019
A rhabdomyosarcoma cell migration inhibitor screen using phase-contrast microscopy
Birgitte Bjørnerud1, Jørgen Wesche2, Ellen Margrethe Haugsten1
1Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
This study developed a computational tool to screen inhibitors for rhabdomyosarcoma (RMS) cell migration. Targeting MAPK and PI3K pathways decreased migration, while ROCK and FAK inhibition surprisingly increased it by altering cell adhesion.
Area of Science:
- Oncology
- Cell Biology
- Bioinformatics
Background:
- Rhabdomyosarcoma (RMS) is a pediatric soft tissue cancer.
- Fibroblast growth factor receptor 4 (FGFR4) pathway alterations correlate with RMS metastasis and poor prognosis.
- Cancer cell migration and invasion are key features of metastatic disease.
Purpose of the Study:
- To develop a computational tool for analyzing cell migration velocity in phase contrast images.
- To conduct a high-throughput inhibitor screen targeting signaling pathways in RMS cells with active FGFR4.
- To identify novel therapeutic targets for modulating RMS cell migration and survival.
Main Methods:
- Development of an automated computational tool for tracking and measuring cell migration velocity.
- Implementation of a large-scale inhibitor screen (462 compounds) on approximately 700,000 RMS-derived cells (RMS559) with constitutively active FGFR4.
- Validation of inhibitor effects on cell migration and viability, focusing on Receptor Tyrosine Kinases (RTKs), Mitogen-Activated Protein Kinases (MAPK), and Phosphoinositide 3-Kinases (PI3K) pathways.
Main Results:
- Inhibitors of MAPK and PI3K pathways reduced RMS cell migration and, in some cases, cell viability.
- FGFR4 inhibition decreased RMS559 cell migration.
- Unexpectedly, Rho-associated protein kinase (ROCK) and focal adhesion kinase (FAK) inhibitors increased RMS559 cell migration by reducing focal adhesions.
Conclusions:
- Targeting specific signaling pathways can modulate the migration and survival of metastatic RMS cells.
- The developed computational tool is effective for large-scale inhibitor screening.
- ROCK and FAK pathways represent potential targets for modulating RMS cell migration, with complex effects on cell adhesion and velocity.
