Angiotensin 1-7 inhibits angiotensin II-stimulated head and neck cancer progression

Angiotensin II (Ang II) is the product of the proteolytic action of angiotensin‐converting enzyme (ACE) on the precursor peptide, angiotensin I (Ang I). In addition to its vasoactive properties, Ang II is able to stimulate angiogenesis and act as a mitogen, promoting cellular proliferation. Recently, evidence has emerged that Ang II is also able to promote tumour invasion, a key step in the metastatic cascade, although the mechanisms by which it does so remain largely obscure. Here we show that Ang II is able to promote the invasion and migration of head and neck squamous cell carcinoma (HNSCC) cells both in an autocrine manner and by triggering stromal tumour‐paracrine interactions. The effects of Ang II on autocrine and paracrine signalling pathways are mediated by angiotensin receptor 1 (AT1R) and inhibited by angiotensin 1‐7 (Ang 1‐7), a peptide produced from Ang II by the action of angiotensin‐converting enzyme 2 (ACE2). These data are the first to demonstrate a role for the renin–angiotensin system in oral carcinogenesis and raise the possibility of utilizing AT1R receptor antagonists and/or Ang 1‐7 as novel therapeutic agents for HNSCC.