Effect of claudin expression on paracellular permeability, migration and invasion of colonic cancer cells

Masaya Takehara, Tomoko Nishimura, Shinji Mima, Tatsuya Hoshino, Tohru Mizushima

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Alteration in the expression of claudins, consisting of tight junctions (TJs), has been reported in various clinically isolated tumors. Claudins play an important role not only in the intercellular barrier function of TJs but also in migration and invasiveness of cancer cells. However, the use of different types of cells and different claudins in these studies has complicated the picture. In this study, we systematically examined the effect of claudin (claudin-1, -2, -3, -4 and -15) overexpression on the paracellular permeability, migration and invasiveness of Caco-2 colonic cancer cells. Overexpression of claudin-4 or claudin-2 increased or decreased, respectively, paracellular permeability. Overexpression of claudin-4 specifically stimulated the invasive activity of the Caco-2 cells. Furthermore, activation of matrix metalloproteinase (MMP)-2 and MMP-9 were observed in the claudin-4- overexpressing cells, suggesting that the invasive activity was stimulated through an increase in MMP activity. Overexpression of claudin-2 or claudin-3 and -4 stimulated or inhibited, respectively, the migration activity of the Caco-2 cells. Immunostaining analysis revealed that each of the overexpressed claudins localized at TJs under the conditions used to evaluate paracellular permeability. In contrast, they localized mainly in intracellu- lar compartments under experimental conditions designed to assess cell invasion and migration. Overall, the results of this study show that the effect exerted by the claudins on the intercellular barrier function of TJs, as well as on cell migration and invasive activity, differs depending on the particular claudin species. Furthermore, the subcellular localization of the claudins varies according to the culture conditions.

Original languageEnglish
Pages (from-to)825-831
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume32
Issue number5
DOIs
Publication statusPublished - 2009 May
Externally publishedYes

Fingerprint

Claudins
Claudin-4
Colonic Neoplasms
Permeability
Claudin-2
Tight Junctions
Caco-2 Cells
Cell Movement
Claudin-3
Claudin-1
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Neoplasms

Keywords

  • Cancer
  • Claudin
  • Invasion
  • Permeability
  • Tight junction

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology

Cite this

Effect of claudin expression on paracellular permeability, migration and invasion of colonic cancer cells. / Takehara, Masaya; Nishimura, Tomoko; Mima, Shinji; Hoshino, Tatsuya; Mizushima, Tohru.

In: Biological and Pharmaceutical Bulletin, Vol. 32, No. 5, 05.2009, p. 825-831.

Research output: Contribution to journalArticle

Takehara, Masaya ; Nishimura, Tomoko ; Mima, Shinji ; Hoshino, Tatsuya ; Mizushima, Tohru. / Effect of claudin expression on paracellular permeability, migration and invasion of colonic cancer cells. In: Biological and Pharmaceutical Bulletin. 2009 ; Vol. 32, No. 5. pp. 825-831.
@article{68545df9a7e641f9a16628253a9dffaa,
title = "Effect of claudin expression on paracellular permeability, migration and invasion of colonic cancer cells",
abstract = "Alteration in the expression of claudins, consisting of tight junctions (TJs), has been reported in various clinically isolated tumors. Claudins play an important role not only in the intercellular barrier function of TJs but also in migration and invasiveness of cancer cells. However, the use of different types of cells and different claudins in these studies has complicated the picture. In this study, we systematically examined the effect of claudin (claudin-1, -2, -3, -4 and -15) overexpression on the paracellular permeability, migration and invasiveness of Caco-2 colonic cancer cells. Overexpression of claudin-4 or claudin-2 increased or decreased, respectively, paracellular permeability. Overexpression of claudin-4 specifically stimulated the invasive activity of the Caco-2 cells. Furthermore, activation of matrix metalloproteinase (MMP)-2 and MMP-9 were observed in the claudin-4- overexpressing cells, suggesting that the invasive activity was stimulated through an increase in MMP activity. Overexpression of claudin-2 or claudin-3 and -4 stimulated or inhibited, respectively, the migration activity of the Caco-2 cells. Immunostaining analysis revealed that each of the overexpressed claudins localized at TJs under the conditions used to evaluate paracellular permeability. In contrast, they localized mainly in intracellu- lar compartments under experimental conditions designed to assess cell invasion and migration. Overall, the results of this study show that the effect exerted by the claudins on the intercellular barrier function of TJs, as well as on cell migration and invasive activity, differs depending on the particular claudin species. Furthermore, the subcellular localization of the claudins varies according to the culture conditions.",
keywords = "Cancer, Claudin, Invasion, Permeability, Tight junction",
author = "Masaya Takehara and Tomoko Nishimura and Shinji Mima and Tatsuya Hoshino and Tohru Mizushima",
year = "2009",
month = "5",
doi = "10.1248/bpb.32.825",
language = "English",
volume = "32",
pages = "825--831",
journal = "Biological and Pharmaceutical Bulletin",
issn = "0918-6158",
publisher = "Pharmaceutical Society of Japan",
number = "5",

}

TY - JOUR

T1 - Effect of claudin expression on paracellular permeability, migration and invasion of colonic cancer cells

AU - Takehara, Masaya

AU - Nishimura, Tomoko

AU - Mima, Shinji

AU - Hoshino, Tatsuya

AU - Mizushima, Tohru

PY - 2009/5

Y1 - 2009/5

N2 - Alteration in the expression of claudins, consisting of tight junctions (TJs), has been reported in various clinically isolated tumors. Claudins play an important role not only in the intercellular barrier function of TJs but also in migration and invasiveness of cancer cells. However, the use of different types of cells and different claudins in these studies has complicated the picture. In this study, we systematically examined the effect of claudin (claudin-1, -2, -3, -4 and -15) overexpression on the paracellular permeability, migration and invasiveness of Caco-2 colonic cancer cells. Overexpression of claudin-4 or claudin-2 increased or decreased, respectively, paracellular permeability. Overexpression of claudin-4 specifically stimulated the invasive activity of the Caco-2 cells. Furthermore, activation of matrix metalloproteinase (MMP)-2 and MMP-9 were observed in the claudin-4- overexpressing cells, suggesting that the invasive activity was stimulated through an increase in MMP activity. Overexpression of claudin-2 or claudin-3 and -4 stimulated or inhibited, respectively, the migration activity of the Caco-2 cells. Immunostaining analysis revealed that each of the overexpressed claudins localized at TJs under the conditions used to evaluate paracellular permeability. In contrast, they localized mainly in intracellu- lar compartments under experimental conditions designed to assess cell invasion and migration. Overall, the results of this study show that the effect exerted by the claudins on the intercellular barrier function of TJs, as well as on cell migration and invasive activity, differs depending on the particular claudin species. Furthermore, the subcellular localization of the claudins varies according to the culture conditions.

AB - Alteration in the expression of claudins, consisting of tight junctions (TJs), has been reported in various clinically isolated tumors. Claudins play an important role not only in the intercellular barrier function of TJs but also in migration and invasiveness of cancer cells. However, the use of different types of cells and different claudins in these studies has complicated the picture. In this study, we systematically examined the effect of claudin (claudin-1, -2, -3, -4 and -15) overexpression on the paracellular permeability, migration and invasiveness of Caco-2 colonic cancer cells. Overexpression of claudin-4 or claudin-2 increased or decreased, respectively, paracellular permeability. Overexpression of claudin-4 specifically stimulated the invasive activity of the Caco-2 cells. Furthermore, activation of matrix metalloproteinase (MMP)-2 and MMP-9 were observed in the claudin-4- overexpressing cells, suggesting that the invasive activity was stimulated through an increase in MMP activity. Overexpression of claudin-2 or claudin-3 and -4 stimulated or inhibited, respectively, the migration activity of the Caco-2 cells. Immunostaining analysis revealed that each of the overexpressed claudins localized at TJs under the conditions used to evaluate paracellular permeability. In contrast, they localized mainly in intracellu- lar compartments under experimental conditions designed to assess cell invasion and migration. Overall, the results of this study show that the effect exerted by the claudins on the intercellular barrier function of TJs, as well as on cell migration and invasive activity, differs depending on the particular claudin species. Furthermore, the subcellular localization of the claudins varies according to the culture conditions.

KW - Cancer

KW - Claudin

KW - Invasion

KW - Permeability

KW - Tight junction

UR - http://www.scopus.com/inward/record.url?scp=66749153752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66749153752&partnerID=8YFLogxK

U2 - 10.1248/bpb.32.825

DO - 10.1248/bpb.32.825

M3 - Article

C2 - 19420749

AN - SCOPUS:66749153752

VL - 32

SP - 825

EP - 831

JO - Biological and Pharmaceutical Bulletin

JF - Biological and Pharmaceutical Bulletin

SN - 0918-6158

IS - 5

ER -