Possible correlation of sonic hedgehog signaling with epithelial–mesenchymal transition in muscle-invasive bladder cancer progression

Koichi Kitagawa, Katsumi Shigemura, Shian Ying Sung, Kuan Chou Chen, Chao Ching Huang, Yi Te Chiang, Ming Che Liu, Tzu Wen Huang, Fukashi Yamamichi, Toshiro Shirakawa, Masato Fujisawa

研究成果: 雜誌貢獻文章

摘要

Purpose: To investigate the role of sonic hedgehog (Shh) signaling and epithelial–mesenchymal transition (EMT) in bladder cancer progression and invasion. Methods: We cultured three bladder cancer cell lines, muscle-invasive T24 and 5637, and non-muscle-invasive KK47, in the presence of a recombinant-Shh (r-Shh) protein or cyclopamine, a Shh signaling inhibitor, to investigate proliferation and expression of EMT markers. Wound-healing assays and transwell assay were performed to evaluate cell invasion and migration. Mice were then inoculated with bladder cancer cells and treated with cyclopamine. Mouse tumor samples were stained for Shh signaling and EMT markers. Results: R-Shh protein enhanced cell proliferation, whereas cyclopamine significantly suppressed cell proliferation, especially in invasive cancer (5637 and T24) (p < 0.05). R-Shh protein promoted EMT, suppressed E-cadherin and enhanced N-cadherin and vimentin and Gli1, an Shh downstream molecule, while cyclopamine blocked EMT, especially in 5637 and T24. Cyclopamine also inhibited cell invasion and migration in vitro. In the animal study, intraperitoneal injection of cyclopamine significantly suppressed tumor growth in 5637 and T24 in mice (p = 0.01 and p = 0.004, respectively) and slightly suppressing KK47 tumor growth (p = 0.298). Significant cyclopamine-induced suppression of Gli1 in 5637 and T24 mouse tumors (both p = 0.03) was seen, suggesting that muscle-invasive bladder cancer may be more dependent on Shh signaling than non-muscle-invasive bladder cancer. Conclusions: Shh signaling and EMT were especially enhanced in muscle-invasive bladder cancer progression and invasion, and suppressed by the inhibition of Shh signaling.

原文英語
期刊Journal of Cancer Research and Clinical Oncology
DOIs
出版狀態已發佈 - 一月 1 2019

指紋

Hedgehogs
Urinary Bladder Neoplasms
Hedgehog Proteins
Muscles
Cadherins
Neoplasms
Cell Movement
Cell Proliferation
Vimentin
Growth
cyclopamine
Intraperitoneal Injections
Wound Healing
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

@article{71e04ac7b50845119c8bcd34e96d47e4,
title = "Possible correlation of sonic hedgehog signaling with epithelial–mesenchymal transition in muscle-invasive bladder cancer progression",
abstract = "Purpose: To investigate the role of sonic hedgehog (Shh) signaling and epithelial–mesenchymal transition (EMT) in bladder cancer progression and invasion. Methods: We cultured three bladder cancer cell lines, muscle-invasive T24 and 5637, and non-muscle-invasive KK47, in the presence of a recombinant-Shh (r-Shh) protein or cyclopamine, a Shh signaling inhibitor, to investigate proliferation and expression of EMT markers. Wound-healing assays and transwell assay were performed to evaluate cell invasion and migration. Mice were then inoculated with bladder cancer cells and treated with cyclopamine. Mouse tumor samples were stained for Shh signaling and EMT markers. Results: R-Shh protein enhanced cell proliferation, whereas cyclopamine significantly suppressed cell proliferation, especially in invasive cancer (5637 and T24) (p < 0.05). R-Shh protein promoted EMT, suppressed E-cadherin and enhanced N-cadherin and vimentin and Gli1, an Shh downstream molecule, while cyclopamine blocked EMT, especially in 5637 and T24. Cyclopamine also inhibited cell invasion and migration in vitro. In the animal study, intraperitoneal injection of cyclopamine significantly suppressed tumor growth in 5637 and T24 in mice (p = 0.01 and p = 0.004, respectively) and slightly suppressing KK47 tumor growth (p = 0.298). Significant cyclopamine-induced suppression of Gli1 in 5637 and T24 mouse tumors (both p = 0.03) was seen, suggesting that muscle-invasive bladder cancer may be more dependent on Shh signaling than non-muscle-invasive bladder cancer. Conclusions: Shh signaling and EMT were especially enhanced in muscle-invasive bladder cancer progression and invasion, and suppressed by the inhibition of Shh signaling.",
keywords = "Basic study, Bladder cancer, Epithelial–mesenchymal transition, Oncology, Sonic hedgehog",
author = "Koichi Kitagawa and Katsumi Shigemura and Sung, {Shian Ying} and Chen, {Kuan Chou} and Huang, {Chao Ching} and Chiang, {Yi Te} and Liu, {Ming Che} and Huang, {Tzu Wen} and Fukashi Yamamichi and Toshiro Shirakawa and Masato Fujisawa",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00432-019-02987-z",
language = "English",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Possible correlation of sonic hedgehog signaling with epithelial–mesenchymal transition in muscle-invasive bladder cancer progression

AU - Kitagawa, Koichi

AU - Shigemura, Katsumi

AU - Sung, Shian Ying

AU - Chen, Kuan Chou

AU - Huang, Chao Ching

AU - Chiang, Yi Te

AU - Liu, Ming Che

AU - Huang, Tzu Wen

AU - Yamamichi, Fukashi

AU - Shirakawa, Toshiro

AU - Fujisawa, Masato

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: To investigate the role of sonic hedgehog (Shh) signaling and epithelial–mesenchymal transition (EMT) in bladder cancer progression and invasion. Methods: We cultured three bladder cancer cell lines, muscle-invasive T24 and 5637, and non-muscle-invasive KK47, in the presence of a recombinant-Shh (r-Shh) protein or cyclopamine, a Shh signaling inhibitor, to investigate proliferation and expression of EMT markers. Wound-healing assays and transwell assay were performed to evaluate cell invasion and migration. Mice were then inoculated with bladder cancer cells and treated with cyclopamine. Mouse tumor samples were stained for Shh signaling and EMT markers. Results: R-Shh protein enhanced cell proliferation, whereas cyclopamine significantly suppressed cell proliferation, especially in invasive cancer (5637 and T24) (p < 0.05). R-Shh protein promoted EMT, suppressed E-cadherin and enhanced N-cadherin and vimentin and Gli1, an Shh downstream molecule, while cyclopamine blocked EMT, especially in 5637 and T24. Cyclopamine also inhibited cell invasion and migration in vitro. In the animal study, intraperitoneal injection of cyclopamine significantly suppressed tumor growth in 5637 and T24 in mice (p = 0.01 and p = 0.004, respectively) and slightly suppressing KK47 tumor growth (p = 0.298). Significant cyclopamine-induced suppression of Gli1 in 5637 and T24 mouse tumors (both p = 0.03) was seen, suggesting that muscle-invasive bladder cancer may be more dependent on Shh signaling than non-muscle-invasive bladder cancer. Conclusions: Shh signaling and EMT were especially enhanced in muscle-invasive bladder cancer progression and invasion, and suppressed by the inhibition of Shh signaling.

AB - Purpose: To investigate the role of sonic hedgehog (Shh) signaling and epithelial–mesenchymal transition (EMT) in bladder cancer progression and invasion. Methods: We cultured three bladder cancer cell lines, muscle-invasive T24 and 5637, and non-muscle-invasive KK47, in the presence of a recombinant-Shh (r-Shh) protein or cyclopamine, a Shh signaling inhibitor, to investigate proliferation and expression of EMT markers. Wound-healing assays and transwell assay were performed to evaluate cell invasion and migration. Mice were then inoculated with bladder cancer cells and treated with cyclopamine. Mouse tumor samples were stained for Shh signaling and EMT markers. Results: R-Shh protein enhanced cell proliferation, whereas cyclopamine significantly suppressed cell proliferation, especially in invasive cancer (5637 and T24) (p < 0.05). R-Shh protein promoted EMT, suppressed E-cadherin and enhanced N-cadherin and vimentin and Gli1, an Shh downstream molecule, while cyclopamine blocked EMT, especially in 5637 and T24. Cyclopamine also inhibited cell invasion and migration in vitro. In the animal study, intraperitoneal injection of cyclopamine significantly suppressed tumor growth in 5637 and T24 in mice (p = 0.01 and p = 0.004, respectively) and slightly suppressing KK47 tumor growth (p = 0.298). Significant cyclopamine-induced suppression of Gli1 in 5637 and T24 mouse tumors (both p = 0.03) was seen, suggesting that muscle-invasive bladder cancer may be more dependent on Shh signaling than non-muscle-invasive bladder cancer. Conclusions: Shh signaling and EMT were especially enhanced in muscle-invasive bladder cancer progression and invasion, and suppressed by the inhibition of Shh signaling.

KW - Basic study

KW - Bladder cancer

KW - Epithelial–mesenchymal transition

KW - Oncology

KW - Sonic hedgehog

UR - http://www.scopus.com/inward/record.url?scp=85069942397&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069942397&partnerID=8YFLogxK

U2 - 10.1007/s00432-019-02987-z

DO - 10.1007/s00432-019-02987-z

M3 - Article

AN - SCOPUS:85069942397

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

SN - 0171-5216

ER -