title: Resistance of the human colon carcinoma cell line HCT-8 to methotrexate results in selection of cells with features of enterocytic differentiation.
abstract: Results obtained previously with the human colon carcinoma cell line HT-29 have shown that the ability of the cells to develop resistance against methotrexate (MTX) or 5-fluorouracil is restricted to cells committed to differentiate. With the aim of investigating whether this observation is cell type-specific or more general, we have extended our studies to another colon cell line, HCT-8. We have compared HCT-8 parental cells and the MTX-resistant subline HCT8-MTX using transmission electron microscopy and immuno-fluorescence detection of markers of cell polarity and differentiation. Post-confluent parental HCT-8 cells appeared highly heterogeneous and occurred in clusters of piled-up cells in which the majority were unpolarized and undifferentiated, with a minority exhibiting features of enterocyte-like cells. In contrast, HCT8-MTX cells formed domes and appeared as a monolayer of polarized cells with tight junctions and a discrete apical brush border which expressed villin, dipeptidylpeptidase-IV, CEA and the epithelial mucin MUC1. Together, our results suggest that, as in HT-29 cells, induction of resistance to MTX of HCT-8 cells results in the selection of differentiated cell types.
authors.affiliation: INSERM U178, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Barbat
authors.forename: I
authors.initials: I
authors.lastname: Pandrea
authors.forename: D
authors.initials: D
authors.lastname: Cambier
authors.forename: A
authors.initials: A
authors.lastname: Zweibaum
authors.forename: T
authors.initials: T
authors.lastname: Lesuffleur
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D018396:Mucin-1 / Q000378:metabolism; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; D018396:Mucin-1; C026615:villin; D018819:Dipeptidyl Peptidase 4; D008727:Methotrexate