Gastric cancer cell lines as models to study human digestive functions.
The present investigation aims at defining the functional status of several gastric cancer cell lines in order to assess their usefulness as adequate cellular models to study the regulation of gastric digestive functions. Compared to AGS, Hs746t and KATO-III cells, NCI-N87 exhibited an unique differentiation status. They formed coherent monolayers expressing E-cadherin and ZO-1 junctional proteins; their integrity and epithelial morphology were maintained at post-confluency for up to 10 days. All cell lines synthesized PAS-reactive (mucous-type) glycoconjugates. However, only NCI-N87 cells expressed MUC6 glycoprotein suggesting a mucopeptic phenotype. Immunostaining, enzymatic assays, Western blotting and Reverse Transcriptase polymerase chain reaction (RT-PCR) revealed that all cell lines contained varying levels of pepsinogen (Pg5) and human gastric lipase (HGL). Only NCI-N87 cells were able to express zymogens at higher levels, in granule-like structures, and to efficiently secrete both HGL and Pg5. The addition of epidermal growth factor (EGF) to post-confluent NCI-N87 cells, which exhibit an abundant membrane staining for EGF-receptors, modulated HGL activity without affecting Pg5. In conclusion, this investigation enlightens the potential usefulness of the gastric cell line NCI-N87 as a model for elucidating the cellular and molecular mechanisms involved in the regulation of human gastric epithelial functions.
CIHR Research Group on Functional Development and Physiopathology of the Digestive Tract, Department of Anatomy & Cell Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
J R
JR
Basque
M
M
Chénard
P
P
Chailler
D
D
Ménard
D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D002454:Cell Differentiation; D002455:Cell Division; D004063:Digestion / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000096:biosynthesis; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008049:Lipase / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D055272:Mucin-6; D009077:Mucins / Q000096:biosynthesis; D010434:Pepsin A / Q000378:metabolism; D020116:Pepsinogen A / Q000096:biosynthesis; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000201:enzymology; D013274:Stomach Neoplasms / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D062826:Zonula Occludens-1 Protein
D015820:Cadherins; C524734:MUC6 protein, human; D008565:Membrane Proteins; D055272:Mucin-6; D009077:Mucins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D004815:Epidermal Growth Factor; D020116:Pepsinogen A; D008049:Lipase; D010434:Pepsin A