The cell-surface serine protease prostasin is lost during cervical squamous cell carcinogenesis

Abstract

The glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin has been reported to have increased expression with tumor-promoting properties in some cancer types, while expression is lost and prostasin displays tumor-suppressing properties in other cancer types. Due to these context-dependent and opposing expression patterns and functions of prostasin, characterization of each cancer type is important. In the present study, we aimed to determine the expression of prostasin in the normal cervix and in cervical squamous cell carcinoma (CSCC), the most common type of cervical cancer. We found that prostasin protein is expressed in both murine and human cervix and is consistently localized on the cell surface in suprabasal layers of squamous cells in healthy cervical epithelia. To assess whether prostasin protein is differentially expressed during cervical carcinogenesis, we performed a comprehensive immunohistochemical analysis of prostasin protein expression levels and localization in tissue arrays of paraffin-embedded human cervical carcinomas compared to the corresponding normal tissue. Prostasin protein is expressed in the well-differentiated cellular strata with expression patterns similar to pan-keratin and E-cadherin, and is lost during the dedifferentiation of epithelial cells, a hallmark of high-grade CSCC. The prostasin expression profile, with differential expression in cancer, provide valuable information that may give clues to the function(s) of this protease in normal epithelial biology and carcinogenesis.

Keywords: Cell surface serine protease; Cervical squamous cell carcinoma; PRSS8; Prostasin.