Modulation of cell adhesion molecules in various epithelial cell lines after treatment with PP2.
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.
Calcagno
Anna Maria
AM
Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA. calcagnoa@mail.nih.gov
Fostel
Jennifer M
JM
Orchekowski
Randal P
RP
Alston
James T
JT
Mattes
William B
WB
Siahaan
Teruna J
TJ
Ware
Joseph A
JA
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*
C412373:AG 1879; C568122:CLDN3 protein, human; D015820:Cadherins; D062465:Claudin-3; D008565:Membrane Proteins; D011743:Pyrimidines; D012333:RNA, Messenger; D019061:src-Family Kinases