Down-regulation of HAI-1 is associated with poor-differentiation status of colorectal cancer

Abstract

Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a Kunitz-type serine protease inhibitor which is widely expressed in epithelial cells. The purpose of this study is to investigate the relationship between HAI-1 expression and differentiation status of colorectal epithelia. The expression of HAI-1 in clinical samples of both cancerous and normal colorectal tissues was evaluated by immunohistochemical staining. An in vitro epithelial differentiation model of Caco-2 cell was established, and the characteristics of differentiation of Caco-2 cells were observed by transmission electron microscopy. The expression of HAI-1 in Caco-2 cells at different differentiation stages was examined by western blot. Immunohistochemical staining of 52 human colorectal cancer tissues showed a definite correlation between HAI-1 expression and differentiation status: IHC score (mean±SE) of HAI-1 was higher for well- or moderately-differentiated colorectal cancer tissues than for poorly-differentiated colorectal cancer tissues, with significant differences in HAI-1 positive rate (P<0.01 and P<0.05 for well-differentiated vs. poorly-differentiated and moderately-differentiated vs. poorly-differentiated, respectively). Immunohistochemical staining of normal colorectal tissues showed positive HAI-1 expression in well-differentiated epithelial cells whereas the under-differentiated crypt cells showed very weak HAI-1 staining signals. The result of western blot also showed the gradual increasing of HAI-1 expression during the process of Caco-2 differentiation in vitro. HAI-1 expression correlates with the differentiation status of colorectal epithelia and could serve as a differentiation marker.