Cargando…

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

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 c...

Descripción completa

Detalles Bibliográficos
Autores principales: Segal, Dagan, Mazloom-Farsibaf, Hanieh, Chang, Bo-Jui, Roudot, Philippe, Rajendran, Divya, Daetwyler, Stephan, Fiolka, Reto, Warren, Mikako, Amatruda, James F., Danuser, Gaudenz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516844/
https://www.ncbi.nlm.nih.gov/pubmed/36155740
http://dx.doi.org/10.1083/jcb.202109100
Descripción
Sumario: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.