SPLUNC1 (PLUNC) is expressed in glandular tissues of the respiratory tract and in lung tumours with a glandular phenotype

Abstract

Short PLUNC1 (SPLUNC1) is the founding member of a novel family of proteins (PLUNC) expressed in the upper respiratory tract that may function in host defence. It is one of the most highly expressed genes in the upper airways and the protein has been detected in sputum and nasal secretions. This study describes, for the first time, the precise cellular localization of SPLUNC1 in human tissues from the respiratory tract. Although SPLUNC1 is found in some epithelial cells of the upper airways and coats the surface epithelial cell lining of the major airways, the most significant site of protein localization is in mucous cells and ducts of submucosal glands. Intense staining is also seen in minor glands of the nose, sinuses, posterior tongue and tonsil, suggesting that the protein is secreted into mucoid secretions of these tissues, where it probably functions in host defence. No staining was seen in peripheral lung tissue. As SPLUNC1 has been suggested to be a novel lung cancer marker, a limited panel of lung cancers was also studied. The findings suggest that SPLUNC1 is commonly expressed in adenocarcinomas, muco-epidermoid carcinoma, and bronchio-alveloar carcinoma, and is absent from small-cell carcinoma and squamous cell carcinoma. This expression pattern is consistent with the presumed phenotypic origin of these tumours and suggests that SPLUNC1 may be a useful marker for lung cancer.

SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage

“…The original PLUNC gene, which is now called SPLUNC1, comprises up to 10% of total protein in the airway surface liquid, and can readily be detected in both nasal lavage and tracheal secretions (14)(15)(16). SPLUNC1 is expressed in both submucosal glands, the superficial epithelia and in neutrophils, and in theory, is present in the correct regions of the lung to be a volume sensing molecule, because it can be secreted onto the mucosal surface of the superficial epithelial where ENaC is expressed (17,18). Thus, because SPLUNC1 bound to trypsin, we initiated studies to better characterize SPLUNC1 function and to determine whether it was a soluble regulator of ENaC.…”

Gene expression profiling with microarray and SAGE identifies PLUNC as a marker for hepatoid adenocarcinoma of the stomach

“…14 Immunohistochemical analysis of PLUNC in lung cancer revealed that PLUNC is commonly expressed in adenocarcinoma, mucoepidermoid carcinoma, and bronchoalveolar carcinoma and is absent from small cell carcinoma and squamous cell carcinoma. 15 Although PLUNC is a major secreted protein product in the upper respiratory tract, 15 the biologic function of PLUNC is poorly understood.…”

Proteomic analysis of pediatric sinonasal secretions shows increased MUC5B mucin in CRS

“…Other proteomic studies identified high expression of BPIFA1 in CRS nasal mucosa tissue and verified this observation by immunohistochemistry (16). Since BPIFA1 is well expressed in submucosal glands in the respiratory tract (21,22), its overexpression in CRS sinonasal secretions further supports submucosal gland hyperplasia in CRS sinus mucosa. DMBT1, also known as GP340, is a glycoprotein implicated in immune response (23), mucosal inflammation and epithelial regeneration (24).…”