Transforming Growth Factor-β Promotes Morphomechanical Effects Involved in Epithelial to Mesenchymal Transition in Living Hepatocellular Carcinoma

Mariafrancesca Cascione, Stefano Leporatti, Francesco Dituri, Gianluigi Giannelli

Research output: Contribution to journalArticle

Abstract

The epithelial mesenchymal transition (EMT) is a physiological multistep process involving epithelial cells acquiring a mesenchymal-like phenotype. It is widely demonstrated that EMT is linked to tumor progression and metastasis. The transforming growth factor (TGF)-β pathways have been widely investigated, but its role in the hepatocarcinoma EMT is still unclear. While the biochemical pathways have been extensively studied, the alteration of biomechanical behavior correlated to cellular phenotype and motility is not yet fully understood. To better define the involvement of TGF-β1 in the metastatic progression process in different hepatocarcinoma cell lines (HepG2, PLC/PRF/5, HLE), we applied a systematic morphomechanical approach in order to investigate the physical and the structural characteristics. In addition, we evaluated the antitumor effect of LY2157299, a TGF-βR1 kinase inhibitor, from a biomechanical point of view, using Atomic Force and Confocal Microscopy. Our approach allows for validation of biological data, therefore it may be used in the future as a diagnostic tool to be combined with conventional biomolecular techniques.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume20
Issue number1
DOIs
Publication statusPublished - Dec 28 2018

Keywords

  • Biomarkers
  • Carcinoma, Hepatocellular/etiology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic/metabolism
  • Cytoskeleton/metabolism
  • Elastic Modulus
  • Epithelial-Mesenchymal Transition
  • Humans
  • Liver Neoplasms/etiology
  • Mechanotransduction, Cellular
  • Microscopy, Atomic Force
  • Neoplasm Grading
  • Transforming Growth Factor beta/metabolism

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