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Last Updated: 01/16/2020

DCTD Scientists Develop a Clinical Monitoring Tool for Epithelial-Mesenchymal Phenotype

Carcinomas can convert from their original epithelial cell-like phenotype to a mesenchymal-like or partial mesenchymal phenotype in a process called epithelial-mesenchymal transition (EMT). This change is thought to promote tumor invasiveness, metastasis, and resistance to chemotherapy.

DCTD Scientists Develop a Clinical Monitoring Tool for Epithelial-Mesenchymal Phenotype

Many of the observations of EMT and its consequences come from studies in cell lines and animal models of cancer; however, because of the difficulty in observing such changes in patients’ tumors, researchers still lack comprehensive understanding of the clinical implications of this transition. A recent publication in Cancer Research describes a new protein-based assay that can evaluate the epithelial-mesenchymal phenotype (i.e., how far along the process of EMT has proceeded) of each cell in a patient’s tumor biopsy.

This standardized microscopic immunofluorescence assay of EMT phenotypic heterogeneity (dubbed the EMT-IFA) provided initial observations of epithelial-mesenchymal phenotype in tumors of patients undergoing cancer treatments. The results demonstrate the possibility of both improved understanding of the clinical importance of EMT and clinical monitoring of tumor adaptation to therapy.

Publication Highlights

  • EMT-IFA analysis was restricted to individual carcinoma cells by the use of the tumor marker β-catenin in combination with cellular morphology. This allowed for mesenchymal-like carcinoma cells to be distinguished from stromal cells, which are normal, non-cancerous cells with a mesenchymal phenotype that exist within many tumors and can confound observations.
  • EMT-IFA monitoring of tumor biopsies from patients with metastatic carcinoma found a wide range of epithelial-mesenchymal phenotypes and spatial distributions, even within groups of patients with the same tumor type. Longitudinal studies that monitor these characteristics in patient tumor biopsies using the EMT-IFA tool could determine the clinical implications of these phenotypic patterns.
  • EMT-IFA analysis of patient biopsies revealed profound changes in the epithelial-mesenchymal phenotypic character of metastatic carcinomas after 1 week of treatment with the tyrosine kinase inhibitor pazopanib. This phenotypic plasticity conferred by EMT enables rapid adaptive response to therapy, which may lead to acquired drug resistance.

Reference

Navas T, Kinders RJ, Lawrence SM, et al. Clinical Evolution of Epithelial-Mesenchymal Transition in Human Carcinomas. Cancer Res. 2020 Jan 15;80(2):304-318.