Increased basolateral sorting of carcinoembryonic antigen in a polarized colon carcinoma cell line after cholesterol depletion-Implications for treatment of inflammatory bowel disease

World J Gastroenterol. 2008 Mar 14;14(10):1528-33. doi: 10.3748/wjg.14.1528.

Abstract

Aim: To investigate a possible increase of basolateral expression of carcinoembryonic antigen (CEA) by interfering with the apical transport machinery, we studied the effect of cholesterol depletion on CEA sorting and secretion.

Methods: Cholesterol depletion was performed in polarized Caco-2 cells using lovastatin and methyl-beta-cyclodextrin.

Results: We show that CEA is predominantly expressed and secreted at the apical surface. Reduction of the cholesterol level of the cell by 40%-50% with lovastatin and methyl-beta-cyclodextrin led to a significant change of the apical-to-basolateral transport ratio towards the basolateral membrane.

Conclusion: As basolateral expression of CEA has been suggested to have anti-inflamatory properties, Cholesterol depletion of enterocytes might be a potential approach to influence the course of inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Anticholesteremic Agents / therapeutic use*
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Caco-2 Cells
  • Carcinoembryonic Antigen / metabolism*
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cholesterol / metabolism*
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / metabolism
  • Lovastatin / therapeutic use
  • beta-Cyclodextrins / therapeutic use*

Substances

  • Anticholesteremic Agents
  • Carcinoembryonic Antigen
  • beta-Cyclodextrins
  • methyl-beta-cyclodextrin
  • Cholesterol
  • Lovastatin