In vivo 3D profiling of site-specific human cancer cell morphotypes in zebrafish

Dagan Segal, Hanieh Mazloom-Farsibaf, Bo Jui Chang, Philippe Roudot, Divya Rajendran, Stephan Daetwyler, Reto P Fiolka, Mikako Warren, James F Amatruda, Gaudenz Danuser

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
JournalThe Journal of cell biology
Volume221
Issue number11
DOIs
StatePublished - Nov 7 2022

ASJC Scopus subject areas

  • Cell Biology

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