TY - JOUR
T1 - In vivo 3D profiling of site-specific human cancer cell morphotypes in zebrafish
AU - Segal, Dagan
AU - Mazloom-Farsibaf, Hanieh
AU - Chang, Bo Jui
AU - Roudot, Philippe
AU - Rajendran, Divya
AU - Daetwyler, Stephan
AU - Fiolka, Reto
AU - Warren, Mikako
AU - Amatruda, James F.
AU - Danuser, Gaudenz
N1 - Publisher Copyright:
© 2022 Segal et al.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.202109100
DO - 10.1083/jcb.202109100
M3 - Article
C2 - 36155740
AN - SCOPUS:85138639354
SN - 0021-9525
VL - 221
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 11
M1 - e202109100
ER -