Abundant expression of the intestinal protein villin in Barrett's metaplasia and esophageal adenocarcinomas

Abstract

Villin is a cytoskeletal protein that is involved in the formation of brush-border microvilli in normal small intestine and colon epithelium. This protein is present in Barrett's metaplasia but is reported not to be expressed in Barrett's adenocarcinoma. In this study, we analyzed villin protein expression in Barrett's metaplasia and in both Barrett's adenocarcinomas and tumors of the gastric cardia. Immunohistochemical analysis was used to evaluate the expression and cellular localization of the villin protein in 21 cases of Barrett's metaplasia, 30 cases of Barrett's adenocarcinoma, 16 cases of gastric cardia adenocarcinoma, and eight cases of adenocarcinoma of the distal esophagus. Southern, northern, and western blot analyses were used to evaluate the potential mechanisms for regulation of villin protein expression. Villin protein expression was observed in 21 of 21 cases (100%) of intestinal-type Barrett's metaplasia and in 28 of 30 cases (93%) of Barrett's adenocarcinoma and was thus highly expressed in these tumors. Northern blot analysis demonstrated villin mRNA (3.5 and 2.7 kb) in both villin-positive Barrett's metaplasia and adenocarcinomas. Western blot analysis with the antibody used for immunohistochemical analysis confirmed the presence of a single villin protein band of 95 kDa. Abundant villin expression also was present in both adenocarcinoma of the gastric cardia (13 of 16 cases; 81%) and distal esophageal adenocarcinomas of unknown origin (six of eight cases; 75%). The intestinal brushborder enzyme sucrase isomaltase was found to be present in only 22 of 46 cases (48%) of the adenocarcinomas that expressed villin. We concluded that the protein villin is highly expressed in Barrett's adenocarcinomas and is well maintained in these and other esophageal tumors.

Claudin-18: a dominant tight junction protein in Barrett's esophagus and likely contributor to its acid resistance

“…As noted in MATERIALS AND METHODS, villin and mucin 2 are established markers of SCE and their presence by qRT-PCR used to ensure that the biopsies analyzed for claudins were derived from BE and not from proximal stomach (20,21,31).…”

“…The diagnosis of BE is confirmed on esophageal biopsy by the presence of goblet cells that stain positive with Alcian blue at pH 2.5 for acidic mucins (29). Biochemically BE is characterized by abundant expression of the intestinal protein villin and mucin 2 (20,21,31). The metaplastic SCE of BE arises in the setting of gastroesophageal reflux disease (GERD) likely as replacement for acid-damaged SqE, and, as such, SCE is more acid resistant than SqE and represents a form of "adaptive protection" against a hostile luminal environment (28).…”

Autotaxin and lysophosphatidic acid stimulate intestinal cell motility by redistribution of the actin modifying protein villin to the developing lamellipodia

“…Villin is an epithelial cell specific actin binding protein that regulates actin reorganization, cell morphology, epithelial-to-mesenchymal transition, cell invasion as well as cell migration indicating the significance of this protein to intestinal and renal cell function [7,8]. The expression of villin gene is maintained in carcinomas derived from intestinal and renal epithelial cells and villin is also expressed in other adenocarcinomas even though it is absent from normal tissue such as Barrett's metaplasia, esophageal adenocarcinomas, gastric cardia adenocarcinomas and in chronic atrophic gastritis [9,10]. Chronic Helicobacter pylori infection has also been shown to induce endogenous villin expression in the stomach [11].…”

Dysplasia in Barrett esophagus

“…In the current study, the combined percentage of indefinite/LGD cases was 10.6%. Diagnostic problems will be lessened by the further development of biomarkers that can better predict which individuals will experience progression to invasive malignancy 29–31. However, until that time, difficulties with the pathologic diagnosis will continue to represent a challenge in chemoprevention studies.…”