Apolipoprotein E and colon cancer. Expression in normal and malignant human intestine and effect on cultured human colonic adenocarcinoma cells.
Background: Apolipoprotein E (apo E) is a key regulatory protein in lipoprotein metabolism and it is also a potent inhibitor of cell proliferation. Although genetic alterations of apo E affect enterohepatic cholesterol transport and, presumably, the risk of colon carcinoma, the expression and potential functions of apo E in the human intestine are poorly known. Methods: The localization of apo E in normal and malignant gastrointestinal tract was studied using immunohistochemistry and in situ hybridization. The effect of apo E3 on cell polarity and the distribution of beta-catenin was examined in HT29 human colon adenocarcinoma cell lines. Results: Both apo E protein and mRNA were present throughout human intestine. The macrophages in the superficial lamina propria of normal colon were more strongly positive for apo E than those in the small intestine, where the most positively stained cells were dendritic cells and macrophages in the germinal centers of lymphoid follicles. In carcinomas, intensely positive macrophages surrounded the tumor area. In cultured undifferentiated HT29 cells, treatment with apo E improved cell polarity and translocated beta-catenin from the cytoplasm to cell--cell adhesion sites. Conclusions: Mononuclear phagocytes and endocrine cells are the main source of apo E in the gastrointestinal tract. We hypothesize that macrophage-derived apo E may modulate epithelial integrity and thus contribute to cell growth.
Niemi
Mari
M
Department of Internal Medicine, University of Oulu, Kajaanintie 50, FIN-90220, Oulu, Finland
Hakkinen
Tomi
T
Karttunen
Tuomo J.
TJ
Eskelinen
Sinikka
S
Kervinen
Kari
K
Savolainen
Markku J.
MJ
Lehtola
Juhani
J
Makela
Jyrki
J
Yla-Herttuala
Seppo
S
Kesaniemi
Y Antero
YA