Research article

Prostaglandin E2-EP1 and EP2 receptor signaling promotes apical junctional complex disassembly of Caco-2 human colorectal cancer cells

Marcelo N Tanaka¹ , Bruno L Diaz² , Wanderley de Souza³ and Jose A Morgado-Diaz¹

¹Divisão de Biologia Celular, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rua André Cavalcanti 37, 5° Andar, Rio de Janeiro, RJ, CEP: 20230-051, Brazil

²Laboratório Intermediário de Inflamação, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil

³Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, 21941-902, Rio de Janeiro, RJ, Brazil

author email corresponding author email

BMC Cell Biology 2008, 9:63doi:10.1186/1471-2121-9-63

Published:	2 December 2008

Abstract

Background

The apical junctional complex (AJC) is a dynamic structure responsible to maintain epithelial cell-cell adhesions and it plays important functions such as, polarity, mechanical integrity, and cell signaling. Alteration of this complex during pathological events leads to an impaired epithelial barrier by perturbation of the cell-cell adhesion system. Although clinical and experimental data indicate that prostaglandin E₂ (PGE₂) plays a critical function in promoting cell motility and cancer progression, little is known concerning its role in AJC disassembly, an event that takes place at the beginning of colorectal tumorigenesis. Using Caco-2 cells, a cell line derived from human colorectal cancer, we investigated the effects of prostaglandin E₂ (PGE₂) treatment on AJC assembly and function.

Results

Exposition of Caco-2 cells to PGE₂ promoted differential alteration of AJC protein distribution, as evidenced by immunofluorescence and immunoblotting analysis and impairs the barrier function, as seen by a decrease in the transepithelial electric resistance and an increase in the permeability to ruthenium red marker. We demonstrated the involvement of EP1 and EP2 prostaglandin E₂ receptor subtypes in the modulation of the AJC disassembly caused by prostanoid. Furthermore, pharmacological inhibition of protein kinase-C, but not PKA and p38MAPK significantly prevented the PGE₂ effects on the AJC disassembly.

Conclusion

Our findings strongly suggest a central role of Prostaglandin E2-EP1 and EP2 receptor signaling to mediate AJC disassembly through a mechanism that involves PKC and claudin-1 as important target for the TJ-related effects in human colorectal cancer cells (Caco-2).