TGFbeta1 -mediated epithelial to mesenchymal transition is accompanied by invasion in the SiHa cell line

Eur J Cell Biol. 2002 Aug;81(8):457-68. doi: 10.1078/0171-9335-00265.

Abstract

It has recently been suggested by several investigators that the epithelial-mesenchymal transition-inducing capacity of TGFbetas contributes to invasive transition of tumors at later stages of carcinogenesis. In the present study, we examined the possibility of TGFbeta1-stimulated epithelial-mesenchymal transition in SiHa cell line, detailed molecular events in the process, and its possible contribution to the invasive transition of tumors. TGFbeta1-induced epithelial-mesenchymal transition of SiHa cells was based on morphological and biochemical criteria; actin stress fiber formation, focal translocalization of integrin alphav, talin, and vinculin, fibronectin-based matrix assembly at the cell periphery, and translocalization and down-regulation of E-cadherin. TGFbeta1 also stimulated surface expression of integrin alphavbeta3 and FAK activation. Focal translocalization of integrin alphav preceded actin reorganization and fibronectin matrix assembly, and functional blocking of the integrin suppressed actin stress fiber formation. Furthermore, induction of actin reorganization and fibronectin matrix assembly by TGFbeta1 were shown to be mutually independent events. These changes were irreversible because 5 minutes pulse exposure to TGFbeta1 was sufficient to stimulate progress of actin reorganization and fibronectin matrix assembly. In further studies with raft culture, TGFbeta1 was found to stimulate invasion of SiHa cells into a type I collagen gel matrix. In conclusion, TGFbeta1 stimulated epithelial-mesenchymal transition of SiHa cells, indicating a positive role in the invasive transition of tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / drug effects
  • Actins / metabolism
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Carcinoma / physiopathology
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Size / drug effects
  • Cell Size / physiology
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Cytoskeletal Proteins / drug effects
  • Cytoskeletal Proteins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Extracellular Matrix Proteins / drug effects
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Fibronectins / drug effects
  • Fibronectins / metabolism
  • Humans
  • Integrin alphaV / drug effects
  • Integrin alphaV / metabolism
  • Mesoderm / cytology
  • Mesoderm / drug effects
  • Mesoderm / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / physiopathology
  • Stress Fibers / drug effects
  • Stress Fibers / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / physiopathology

Substances

  • Actins
  • Cytoskeletal Proteins
  • Enzyme Inhibitors
  • Extracellular Matrix Proteins
  • Fibronectins
  • Integrin alphaV
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1