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


CONCLUSIONS
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.
Ehehalt
Robert
R
Department of Internal Medicine IV University Hospital, INF410, Heidelberg 69120, Germany. robert_ehehalt@urz.uni-heidelberg.de
Krautter
Markus
M
Zorn
Martin
M
Sparla
Richard
R
Fullekrug
Joachim
J
Kulaksiz
Hasan
H
Stremmel
Wolfgang
W
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018938:Caco-2 Cells; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D008148:Lovastatin / Q000627:therapeutic use; D047392:beta-Cyclodextrins / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D002272:Carcinoembryonic Antigen; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; D008148:Lovastatin