The natriuretic system in human and murine submandibular salivary glands in health and disease: insights from head and neck tumour cases

Introduction: The wide distribution of the atrial natriuretic peptide was paralleled by a similar presence of its receptors, an indication of the wide range of their biological effects beyond the control of the homeostatic process. This study depicts through immunohistochemical and molecular techniques the distribution and modulation of atrial natriuretic peptide and its receptors in human and murine salivary glands. It also highlights some clinical implications of ANP dysregulation. Methods: Human SMG’s tissue samples were biopsied from normal (3), people with benign (2) or with malignant tumors (8). In addition, biopsies were taken from normal mice (10). They were processed by standard methods for routine microscopy and stained with hematoxylin and eosin or periodic acid Schieff. Other tissue sections underwent immunohistochemical staining with various antibodies targeting the ANP system. Results: The expression of the ANP system and its receptors was detected in the stroma of the submandibular gland (SMG), on the secretory ducts, the nerves supplying the gland and on the smooth muscle of the respective blood vessels. Such an expression was intrinsic and not due to the ectopic blood vessels and nerves. The expression of ANP system receptors was also conserved in the SMG of normal mice. It was up-regulated in primary SMG tumors, in particular, early SMG carcinomas. In case of early stage carcinoma, an inflammatory reaction was detected which could have altered the nerve-parenchymal cell barrier and led to an overwhelming self-limited inflammatory reaction in both stroma and parenchyma. Along the same line, the distribution and up-regulation of the ANP system in the SMG could be a potential clinical marker for some pathologies. In brief, the high production of the ANP and the loss of its receptors in carcinoma could also indicate a paracrine effect of its production in the tumors.