title: Modulation of cell adhesion molecules in various epithelial cell lines after treatment with PP2.
abstract: Regulation and expression of E-cadherin and other adhesion molecules were evaluated after exposure to a selective inhibitor of the Src family of tyrosine kinases and inducer of E-cadherin, PP2. E-cadherin is located within the intercellular junction, and it is involved in the management of paracellular permeability of various epithelial barriers in the body. Epithelial cell lines HCT-116, HT29, Caco-2, LS174T, and ARPE-19 were examined for morphological, functional, protein, and mRNA changes following 20 microM PP2 treatment. PP2 treatment caused cell clustering in Caco-2, HT29, and HCT-116 cells. E-cadherin also redistributed to the points of cell contact in Caco-2 cells. These changes suggest increased E-cadherin-dependent cell adhesion. Studies evaluating transepithelial electrical resistance, an established measurement of paracellular permeability, displayed increases in resistance for the Caco-2 cells following PP2 treatment, which correlates with our microscopy data. In addition, E-cadherin protein levels increased for all cells except HCT-116. ARPE-19 cells did not express E-cadherin at the protein or mRNA level. Expression of adhesion molecules varied for the cell lines, and only Claudin 3 mRNA expression was significantly increased in the three intestinal cell lines treated with PP2. Overall, our data suggest that E-cadherin is positively regulated by inhibition of Src tyrosine kinases at the functional and protein expression levels within these epithelial cell lines.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA. calcagnoa@mail.nih.gov
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Calcagno
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Fostel
authors.forename: Randal P
authors.initials: RP
authors.lastname: Orchekowski
authors.forename: James T
authors.initials: JT
authors.lastname: Alston
authors.forename: William B
authors.initials: WB
authors.lastname: Mattes
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Ware
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D062465:Claudin-3; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: C412373:AG 1879; C568122:CLDN3 protein, human; D015820:Cadherins; D062465:Claudin-3; D008565:Membrane Proteins; D011743:Pyrimidines; D012333:RNA, Messenger; D019061:src-Family Kinases