Role of endothelin receptor signalling in squamous cell carcinoma

Endothelin plays important roles in various physiological functions including vascular constriction. Recent studies reported that the endothelin receptors ET(A) and ET(B) are highly expressed in lung and skin tumor tissues. In contrast, there are few reports on endothelin signalling in the proliferation of head and neck cancer. We found that both ET(A) and ET(B) endothelin receptors were overexpressed in tumor cells of tongue cancer samples by immunohistochemistry. ET(A) and ET(B) were expressed in cultured lingual and esophageal squamous cell carcinoma (SCCs) cell lines. When both cultured cell lines were treated with an ET(A) selective antagonist (BQ123) or an ET(B) selective antagonist (BQ788), inhibition of cell growth was observed. Similar results were observed when SCCs were treated with specific siRNA for the suppression of ET(A) or ET(B). Furthermore, inhibition of the mitogen-activated protein (MAP) kinase pathway by the treatments with ET receptor antagonists and siRNA was also observed. These results indicate that endothelin signalling may, in part, play important roles in cell growth in SCCs through the MAP kinase pathway.