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Resistance of the human colon carcinoma cell line HCT‐8 to methotrexate results in selection of cells with features of enterocytic differentiation
Author(s) -
Barbat Alain,
Pandrea Ivona,
Cambier Danièle,
Zweibaum Alain,
Lesuffleur Thécla
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980302)75:5<731::aid-ijc11>3.0.co;2-9
Subject(s) - cell culture , cancer research , cell , biology , cellular differentiation , carcinoma , microbiology and biotechnology , immunology , genetics , gene
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. Int. J. Cancer 75:731–737, 1998.© 1998 Wiley‐Liss, Inc.