endothelin-1 and Head-and-Neck-Neoplasms

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.

Topics: ADAM Proteins; ADAM17 Protein; Blotting, Western; Carcinoma, Squamous Cell; Cell Communication; Cell Movement; Cells, Cultured; Cyclooxygenase 2; Endothelin-1; Epithelial Cells; ErbB Receptors; Female; Fibroblasts; Head and Neck Neoplasms; Humans; Mouth; Paracrine Communication; Real-Time Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Stromal Cells