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

  • Hinsley E
  • Hunt S
  • Hunter K
 et al. 
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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.

Author-supplied keywords

  • EGFR transactivation
  • endothelin
  • head and neck cancer
  • metastasis
  • migration
  • stromal-epithelial interaction

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