Bile acid induces MUC2 expression and inhibits tumor invasion in gastric carcinomas

Jung Soo Pyo, Young San Ko, Guhyun Kang, Dong Hoon Kim, Woo Ho Kim, Byung Lan Lee, Jin Hee Sohn

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: Bile acids might induce mucin expression and regulate tumor behavior in esophageal and colon cancers. However, little is known about the effect of bile acids on tumor invasiveness of gastric carcinoma (GC). The aim of the current study was to elucidate the mechanisms by which bile acids regulate tumor invasion in GC. Methods: We investigated bile acid-induced MUC2 expression and cell invasion and migration in the cultured GC cell lines, SNU-216, and MKN45. In addition, immunohistochemical analysis of MUC2 and Snail was performed on 389 archival paraffin-embedded tissues of GC to evaluate the correlation of their expression with prognosis. Results: Deoxycholic acid (DCA), a secondary bile acid, had no effect on the viability of SNU-216 and MKN45 GC cells at low concentrations (0–100 μM), but decreased viability at a higher concentration (200 μM). MKN45 cells showed higher MUC2 expression than SNU-216 cells under basal conditions. DCA treatment upregulated MUC2 mRNA expression in both SNU-216 and MKN45 cells. Expression of Snail and MMP9 was markedly decreased by DCA treatment, and E-cadherin expression was subsequently increased. DCA significantly inhibited invasion and migration of SNU-216 and MKN45 cells. In human GC, MUC2 expression showed a negative correlation with Snail expression (P = 0.021) and a significantly positive correlation with better prognosis (P = 0.023). Conclusions: Taken together, our data suggest that DCA induced MUC2 expression in GC cells and inhibited tumor invasion and migration. Additionally, MUC2-expressing GCs showed low rates of Snail expression and were associated with a favorable prognosis.

Original languageEnglish
Article number5
Pages (from-to)1181-1188
Number of pages8
JournalJournal of Cancer Research and Clinical Oncology
Volume141
Issue number7
DOIs
StatePublished - 22 Jul 2015

Fingerprint

Bile Acids and Salts
Deoxycholic Acid
Stomach
Carcinoma
Neoplasms
Snails
Mucins
Cadherins
Esophageal Neoplasms
Paraffin
Colonic Neoplasms
Cell Movement
Cell Line
Messenger RNA

Keywords

  • Deoxycholic acid
  • Gastric carcinoma
  • Invasion
  • MUC2
  • Prognosis

Cite this

Pyo, Jung Soo ; Ko, Young San ; Kang, Guhyun ; Kim, Dong Hoon ; Kim, Woo Ho ; Lee, Byung Lan ; Sohn, Jin Hee. / Bile acid induces MUC2 expression and inhibits tumor invasion in gastric carcinomas. In: Journal of Cancer Research and Clinical Oncology. 2015 ; Vol. 141, No. 7. pp. 1181-1188.
@article{e1aa19a2adf3474cb62f825f72afb08f,
title = "Bile acid induces MUC2 expression and inhibits tumor invasion in gastric carcinomas",
abstract = "Purpose: Bile acids might induce mucin expression and regulate tumor behavior in esophageal and colon cancers. However, little is known about the effect of bile acids on tumor invasiveness of gastric carcinoma (GC). The aim of the current study was to elucidate the mechanisms by which bile acids regulate tumor invasion in GC. Methods: We investigated bile acid-induced MUC2 expression and cell invasion and migration in the cultured GC cell lines, SNU-216, and MKN45. In addition, immunohistochemical analysis of MUC2 and Snail was performed on 389 archival paraffin-embedded tissues of GC to evaluate the correlation of their expression with prognosis. Results: Deoxycholic acid (DCA), a secondary bile acid, had no effect on the viability of SNU-216 and MKN45 GC cells at low concentrations (0–100 μM), but decreased viability at a higher concentration (200 μM). MKN45 cells showed higher MUC2 expression than SNU-216 cells under basal conditions. DCA treatment upregulated MUC2 mRNA expression in both SNU-216 and MKN45 cells. Expression of Snail and MMP9 was markedly decreased by DCA treatment, and E-cadherin expression was subsequently increased. DCA significantly inhibited invasion and migration of SNU-216 and MKN45 cells. In human GC, MUC2 expression showed a negative correlation with Snail expression (P = 0.021) and a significantly positive correlation with better prognosis (P = 0.023). Conclusions: Taken together, our data suggest that DCA induced MUC2 expression in GC cells and inhibited tumor invasion and migration. Additionally, MUC2-expressing GCs showed low rates of Snail expression and were associated with a favorable prognosis.",
keywords = "Deoxycholic acid, Gastric carcinoma, Invasion, MUC2, Prognosis",
author = "Pyo, {Jung Soo} and Ko, {Young San} and Guhyun Kang and Kim, {Dong Hoon} and Kim, {Woo Ho} and Lee, {Byung Lan} and Sohn, {Jin Hee}",
year = "2015",
month = "7",
day = "22",
doi = "10.1007/s00432-014-1890-1",
language = "English",
volume = "141",
pages = "1181--1188",
journal = "Journal of cancer research and clinical oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
number = "7",

}

Bile acid induces MUC2 expression and inhibits tumor invasion in gastric carcinomas. / Pyo, Jung Soo; Ko, Young San; Kang, Guhyun; Kim, Dong Hoon; Kim, Woo Ho; Lee, Byung Lan; Sohn, Jin Hee.

In: Journal of Cancer Research and Clinical Oncology, Vol. 141, No. 7, 5, 22.07.2015, p. 1181-1188.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bile acid induces MUC2 expression and inhibits tumor invasion in gastric carcinomas

AU - Pyo, Jung Soo

AU - Ko, Young San

AU - Kang, Guhyun

AU - Kim, Dong Hoon

AU - Kim, Woo Ho

AU - Lee, Byung Lan

AU - Sohn, Jin Hee

PY - 2015/7/22

Y1 - 2015/7/22

N2 - Purpose: Bile acids might induce mucin expression and regulate tumor behavior in esophageal and colon cancers. However, little is known about the effect of bile acids on tumor invasiveness of gastric carcinoma (GC). The aim of the current study was to elucidate the mechanisms by which bile acids regulate tumor invasion in GC. Methods: We investigated bile acid-induced MUC2 expression and cell invasion and migration in the cultured GC cell lines, SNU-216, and MKN45. In addition, immunohistochemical analysis of MUC2 and Snail was performed on 389 archival paraffin-embedded tissues of GC to evaluate the correlation of their expression with prognosis. Results: Deoxycholic acid (DCA), a secondary bile acid, had no effect on the viability of SNU-216 and MKN45 GC cells at low concentrations (0–100 μM), but decreased viability at a higher concentration (200 μM). MKN45 cells showed higher MUC2 expression than SNU-216 cells under basal conditions. DCA treatment upregulated MUC2 mRNA expression in both SNU-216 and MKN45 cells. Expression of Snail and MMP9 was markedly decreased by DCA treatment, and E-cadherin expression was subsequently increased. DCA significantly inhibited invasion and migration of SNU-216 and MKN45 cells. In human GC, MUC2 expression showed a negative correlation with Snail expression (P = 0.021) and a significantly positive correlation with better prognosis (P = 0.023). Conclusions: Taken together, our data suggest that DCA induced MUC2 expression in GC cells and inhibited tumor invasion and migration. Additionally, MUC2-expressing GCs showed low rates of Snail expression and were associated with a favorable prognosis.

AB - Purpose: Bile acids might induce mucin expression and regulate tumor behavior in esophageal and colon cancers. However, little is known about the effect of bile acids on tumor invasiveness of gastric carcinoma (GC). The aim of the current study was to elucidate the mechanisms by which bile acids regulate tumor invasion in GC. Methods: We investigated bile acid-induced MUC2 expression and cell invasion and migration in the cultured GC cell lines, SNU-216, and MKN45. In addition, immunohistochemical analysis of MUC2 and Snail was performed on 389 archival paraffin-embedded tissues of GC to evaluate the correlation of their expression with prognosis. Results: Deoxycholic acid (DCA), a secondary bile acid, had no effect on the viability of SNU-216 and MKN45 GC cells at low concentrations (0–100 μM), but decreased viability at a higher concentration (200 μM). MKN45 cells showed higher MUC2 expression than SNU-216 cells under basal conditions. DCA treatment upregulated MUC2 mRNA expression in both SNU-216 and MKN45 cells. Expression of Snail and MMP9 was markedly decreased by DCA treatment, and E-cadherin expression was subsequently increased. DCA significantly inhibited invasion and migration of SNU-216 and MKN45 cells. In human GC, MUC2 expression showed a negative correlation with Snail expression (P = 0.021) and a significantly positive correlation with better prognosis (P = 0.023). Conclusions: Taken together, our data suggest that DCA induced MUC2 expression in GC cells and inhibited tumor invasion and migration. Additionally, MUC2-expressing GCs showed low rates of Snail expression and were associated with a favorable prognosis.

KW - Deoxycholic acid

KW - Gastric carcinoma

KW - Invasion

KW - MUC2

KW - Prognosis

UR - http://www.scopus.com/inward/record.url?scp=84938535198&partnerID=8YFLogxK

U2 - 10.1007/s00432-014-1890-1

DO - 10.1007/s00432-014-1890-1

M3 - Article

C2 - 25475007

AN - SCOPUS:84938535198

VL - 141

SP - 1181

EP - 1188

JO - Journal of cancer research and clinical oncology

JF - Journal of cancer research and clinical oncology

SN - 0171-5216

IS - 7

M1 - 5

ER -