In vivo 3D profiling of site-specific human cancer cell morphotypes in zebrafish.
Dagan SegalHanieh Mazloom-FarsibafBo-Jui ChangPhilippe RoudotDivya RajendranStephan DaetwylerReto FiolkaMikako WarrenJames F AmatrudaGaudenz Karl DanuserPublished in: The Journal of cell biology (2022)
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.
Keyphrases
- high resolution
- single cell
- endothelial cells
- cell therapy
- high throughput
- induced apoptosis
- physical activity
- mesenchymal stem cells
- mass spectrometry
- deep learning
- risk assessment
- machine learning
- cell death
- small molecule
- cell cycle arrest
- bone marrow
- cell proliferation
- long non coding rna
- climate change
- amino acid
- protein protein
- pi k akt