Endothelin-1 stimulates motility of head and neck squamous carcinoma cells by promoting stromal-epithelial interactions

Int J Cancer. 2012 Jan 1;130(1):40-7. doi: 10.1002/ijc.25968. Epub 2011 Apr 13.

Abstract

The invasion and migration of cancer cells is increasingly recognised to be influenced by factors derived from adjacent tumour-associated stroma. The contextual signals regulating stromal-tumour interactions, however, remain poorly understood. Here, we identify a role for endothelin-1 (ET-1), a mitogenic peptide elevated in a number of malignancies, in promoting pro-metastatic cross-talk between head and neck cancer cells and adjacent fibroblasts. We demonstrate that treatment of oral fibroblasts with ET-1 activates ADAM17-mediated release of epidermal growth factor receptor (EGFR) ligands, triggering EGFR signalling and increased motility in neighbouring head and neck cancer cells. ET-1-mediated paracrine transactivation of EGFR also increased cyclo-oxygenase-2 levels in the cancer cells, providing a molecular insight into the mechanisms by which the elevated levels of ET-1 observed in head and neck cancers may contribute to disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • ADAM17 Protein
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Communication*
  • Cell Movement / physiology*
  • Cells, Cultured
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Mouth / cytology
  • Mouth / metabolism
  • Paracrine Communication
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*

Substances

  • Endothelin-1
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • EGFR protein, human
  • ErbB Receptors
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human