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Title: Accumulation of transferrin in Caco-2 cells: a possible mechanism of intestinal transferrin absorption. Author: Lim CJ, Norouziyan F, Shen WC. Journal: J Control Release; 2007 Oct 08; 122(3):393-8. PubMed ID: 17586083. Abstract: Transferrin receptor (TfR)-mediated endocytosis and transcytosis in enterocyte-like Caco-2 cells was investigated in order to elucidate the transport mechanism of orally administered Tf-fusion proteins. Cellular uptake and pulse chase studies were performed in Caco-2, MCF-7 and bladder carcinoma (5637) cells using 125I-labeled Tf (125I-Tf). Co-localization studies of Rab 11 and FITC-Tf endocytosed at either the apical or basolateral membrane were performed in polarized Caco-2 cells grown on Transwells, using confocal laser scanning microscopy (LSM510, Zeiss). Unlike in MCF-7 or 5637 cells, where rapid recycling of Tf was observed, a significant amount of endocytosed 125I-Tf accumulated in Caco-2 cells. This accumulation was especially noticeable with the internalization of 125I-Tf from the apical membrane of polarized Caco-2 cells. Confocal microscopy studies showed that apically, but not basolaterally, endocytosed FITC-Tf was delivered to a Rab11-positive compartment. Our results suggest that a significant amount of apically endocytosed Tf in intestinal epithelial cells is transported to a Rab11-positive compartment, possibly a late endosomal and slow recycling compartment. The Rab11-positive compartment may control the release of apically internalized Tf for either slow recycling to apical membrane or processing to transcytotic compartments.[Abstract] [Full Text] [Related] [New Search]