PUBLICATION
In vivo 3D profiling of site-specific human cancer cell morphotypes in zebrafish
- Authors
- Segal, D., Mazloom-Farsibaf, H., Chang, B.J., Roudot, P., Rajendran, D., Daetwyler, S., Fiolka, R., Warren, M., Amatruda, J.F., Danuser, G.
- ID
- ZDB-PUB-220929-4
- Date
- 2022
- Source
- The Journal of cell biology 221(11): (Journal)
- Registered Authors
- Amatruda, James F.
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Disease Models, Animal
- Humans
- Imaging, Three-Dimensional
- Oncogene Proteins, Fusion/genetics
- Sarcoma, Ewing*/genetics
- Sarcoma, Ewing*/pathology
- Tumor Microenvironment
- Zebrafish*
- PubMed
- 36155740 Full text @ J. Cell Biol.
Citation
Segal, D., Mazloom-Farsibaf, H., Chang, B.J., Roudot, P., Rajendran, D., Daetwyler, S., Fiolka, R., Warren, M., Amatruda, J.F., Danuser, G. (2022) In vivo 3D profiling of site-specific human cancer cell morphotypes in zebrafish. The Journal of cell biology. 221(11):.
Abstract
Tissue microenvironments affect the functional states of cancer cells, but determining these influences in vivo has remained a challenge. We present a quantitative high-resolution imaging assay of single cancer cells in zebrafish xenografts to probe functional adaptation to variable cell-extrinsic cues and molecular interventions. Using cell morphology as a surrogate readout of cell functional states, we examine environmental influences on the morphotype distribution of Ewing Sarcoma, a pediatric cancer associated with the oncogene EWSR1-FLI1 and whose plasticity is thought to determine disease outcome through non-genomic mechanisms. Computer vision analysis reveals systematic shifts in the distribution of 3D morphotypes as a function of cell type and seeding site, as well as tissue-specific cellular organizations that recapitulate those observed in human tumors. Reduced expression of the EWSR1-FLI1 protein product causes a shift to more protrusive cells and decreased tissue specificity of the morphotype distribution. Overall, this work establishes a framework for a statistically robust study of cancer cell plasticity in diverse tissue microenvironments.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping