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

• Published in: International journal of cancer Vol. 130; no. 1; pp. 40 - 47
• Main Authors: Hinsley, Emma E., Hunt, Stuart, Hunter, Keith D., Whawell, Simon A., Lambert, Daniel W.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-01-2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: ADAM Proteins - genetics; ADAM Proteins - metabolism; ADAM17 Protein; Biological and medical sciences; Blotting, Western; Cancer; 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; EGFR transactivation; endothelin; Endothelin-1 - genetics; Endothelin-1 - metabolism; Epithelial Cells - metabolism; Epithelial Cells - pathology; Female; Fibroblasts - cytology; Fibroblasts - metabolism; Head & neck cancer; head and neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Medical research; Medical sciences; metastasis; migration; Motility; Mouth - cytology; Mouth - metabolism; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Paracrine Communication; Real-Time Polymerase Chain Reaction; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; RNA, Messenger - genetics; Rodents; Signal Transduction; Stromal Cells - metabolism; Stromal Cells - pathology; stromal-epithelial interaction; Tumors; Cell cell interaction; Endothelin 1; Malignant tumor; Metastasis; Gene expression; Epidermal growth factor receptor; endothelin; Cancerology; EGFR transactivation; migration; ENT disease; Head and neck cancer; Head and neck squamous cell carcinoma; stromal-epithelial interaction; Cell migration; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.25968

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.