Journal Article

Epithelial plasticity can generate multi-lineage phenotypes in human and murine bladder cancers

Elemento, Olivier, Daza, Jorge, Anastos, Harry, Mulholland, David J., Sfakianos, John P., Badani, Ketan K., Bryant, Geoffrey, Galsky, Matthew D., Hu, Yang, Faltas, Bishoy M., Bareja, Rohan

2020

Overview

Tumor heterogeneity is common in cancer, however recent studies have applied single gene expression signatures to classify bladder cancers into distinct subtypes. Such stratification assumes that a predominant transcriptomic signature is sufficient to predict progression kinetics, patient survival and treatment response. We hypothesize that such static classification ignores intra-tumoral heterogeneity and the potential for cellular plasticity occurring during disease development. We have conducted single cell transcriptome analyses of mouse and human model systems of bladder cancer and show that tumor cells with multiple lineage subtypes not only cluster closely together at the transcriptional level but can maintain concomitant gene expression of at least one mRNA subtype. Functional studies reveal that tumor initiation and cellular plasticity can initiate from multiple lineage subtypes. Collectively, these data suggest that lineage plasticity may contribute to innate tumor heterogeneity, which in turn carry clinical implications regarding the classification and treatment of bladder cancer. Recent studies have utilized bulk tumour mRNA sequencing to classify bladder cancers into distinct subgroups. Here, the authors use single cell transcriptomic analysis and cell transplant studies to show that epithelial plasticity can generate basal, luminal and mesenchymal phenotypes in human and murine bladder cancers.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/39 / 631/67 / 631/67/589 / 631/67/589/1336 / 64/60 / Animals / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Bladder / Bladder cancer / Cancer / Cell Lineage - genetics / Cell Plasticity - genetics / Cell Transformation, Neoplastic - genetics / Classification / Developmental plasticity / Functional plasticity / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Gene sequencing / Health services / Heterogeneity / Humanities and Social Sciences / Humans / Integrin alpha6 - genetics / Integrin alpha6 - metabolism / Keratin-5 - genetics / Keratin-5 - metabolism / Mesenchyme / Mice / multidisciplinary / Phenotype / Phenotypes / Phenotypic plasticity / Plastic foam / Plastic properties / Plasticity / Science / Science (multidisciplinary) / Single-Cell Analysis / Subgroups / Transcription / Tumor cells / Tumors / Urinary Bladder Neoplasms - genetics / Urinary Bladder Neoplasms - metabolism / Urinary Bladder Neoplasms - pathology