Abstract
Endothelin plays important roles in various physiological functions including vascular constriction. Recent studies reported that the endothelin receptors ETA and ETB 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 ETA and ETB endothelin receptors were overexpressed in tumor cells of tongue cancer samples by immunohistochemistry. ETA and ETB were expressed in cultured lingual and esophageal squamous cell carcinoma (SCCs) cell lines. When both cultured cell lines were treated with an ETA selective antagonist (BQ123) or an ETB selective antagonist (BQ788), inhibition of cell growth was observed. Similar results were observed when SCCs were treated with specific siRNA for the suppression of ETA or ETB. 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.
Highlights
Endothelin (ET) plays important roles on various physiological functions including vascular constriction [1,2,3,4]
No alterations of integrin α5 and β1 expressions were observed. These results suggest that the cell growth suppression of squamous cell carcinoma (SCC) by the knockdown or blockade of ET receptors is mediated through the direct inhibition of MAPK signalling pathway
There have been several reports on the expression of ET receptors in various human cancers [5,6,7], and it is considered to be the relationship between ET receptor-signalling and tumor cell growth
Summary
Endothelin (ET) plays important roles on various physiological functions including vascular constriction [1,2,3,4]. ET family comprises three isoforms, ET-1, ET-2, and ET-3, that bind to two receptor subtypes, endothelin A (ETA) and endothelin B (ETB) receptors [1,2,3,4]. Recent studies reported that ETA and ETB were highly expressed on lung, colon and skin cancers [5,6,7]. Several reports suggested that ET-1 plays important roles in tumorigenesis, tumor progression, and metastasis Little is known about the role of ET signalling on tumor cell proliferation of oral squamous cell carcinoma (SCC)
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