Cell polarity of the insulin-like growth factor system in human intestinal epithelial cells. Unique apical sorting of insulin-like growth factor binding protein-6 in differentiated human colon cancer cells.
In this study, we have used enterocyte-like differentiated HT29-D4 human colonic carcinoma cells cultured in a glucose-free medium (HT29-D4-GAL cells) on semi-permeable supports in order to investigate the polarity of the insulin-like growth factor (IGF) system. We report that these cells secrete endogenous IGF-II predominantly (66%) from the basolateral cell surface where type I IGF receptors are almost all (> 96%) localized. HT29-D4-GAL cells also secrete IGF-binding protein (IGFBP) -2, -4, and -6 as evidenced by Western ligand and immunoblot analyses of conditioned medium. IGFBP-2 and IGFBP-4 are secreted primarily into the basolateral side (71 and 87%, respectively), whereas IGFBP-6 is targeted to the apical surface (76%) as a possible consequence of an active sorting. Finally, HT29-D4-GAL cells are found to display responses to IGF-II added to the basolateral but not the apical membrane side in terms of intracellular tyrosine phosphorylation and long-term stimulation of amino acid uptake. This study indicates (a) that IGF-II is potentially capable of autocrine regulation on the basolateral side of HT29-D4-GAL cell, and (b) that IGFBP-6 has a unique pattern of secretory polarity. It supports the concept that a differential sorting of the various forms of IGFBPs might play a modulatory role in the maintenance of a functional polarity in the differentiated HT29-D4-GAL cells.
Remacle-Bonnet
M
M
Centre National de la Recherche Scientifique, Unité de Recherches Associée Protéines et Cancer, (URA CNRS-1924), Faculté de Médecine, Marseille, France.
Garrouste
F
F
el Atiq
F
F
Marvaldi
J
J
Pommier
G
G
D000596:Amino Acids / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D016764:Cell Polarity; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000032:analysis; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D002352:Carrier Proteins; D018976:Insulin-Like Growth Factor Binding Protein 6; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1