Objective: The objective of this study was to examine the role of angiotensin II and its metabolites in oral cancer pathogenesis.
Methods: The expression of components of the renin-angiotensin system in normal oral keratinocytes and cells derived from oral dysplasias and oral cancer was determined by qRT-PCR. Oral cancer-derived cell lines SCC4 and H357 or primary oral fibroblasts were treated with Ang II (100 nM) for 4 h in the presence or absence of the Ang II metabolite Ang 1-7 or the angiotensin receptor 1 (AT1R) antagonist telmisartan and the effect on cellular phenotype determined by transwell migration and invasion assays (cancer cells) and wound healing and collagen contraction assays (fibroblasts).
Results: Ang II was able to promote the invasion and migration of oral cancer-derived cells both in an autocrine manner and by triggering stromal-tumour paracrine interactions. The effects of Ang II on autocrine and paracrine signalling pathways were mediated by angiotensin receptor 1 (AT1R) and inhibited by Ang 1-7, a peptide produced from Ang II by the action of angiotensin converting enzyme 2 (ACE2).
Conclusion: These data are the first to demonstrate a role for the renin-angiotensin system in oral carcinogenesis and raise the possibility of utilising AT1R receptor antagonists and/or Ang 1-7 as novel therapeutic agents for oral cancer.