Inhibiting Interleukin-19 Activity Ameliorates Esophageal Squamous Cell Carcinoma Progression

Chung-Hsi Hsing, Franky Antonius Kwok, Hung Chi Cheng, Chien Feng Li, Ming Shi Chang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background:IL-19 is expressed in esophageal squamous cell carcinoma (SCC), but its biological effect on esophageal cancer remains unclear. We determined the correlation between IL-19 expression levels and clinicopathological variables and explored the effects of IL-19 on the esophageal SCC in vivo and in vitro.Methodology/Principal Findings:We determined the expression levels of esophageal SCC tissues from 60 patients using immunohistochemistry. We examined the effects of IL-19 on intracellular signaling, cytokines production as well as proliferation, colonization, and migration in the human esophageal SCC cell line CE81T. Monoclonal antibodies (mAbs) against IL-19 (1BB1) and its receptor IL-20R1 (51D) were used to antagonize the effects of IL-19. We injected SCID mice with CE81T cells and then treated them with anti-IL-19 mAb or control IgG every 3 days and determined tumor growth for 32 days. Of the 60 esophageal SCC patients, 36 patients (60%) were IL-19 strongly stained, which was associated with advanced tumor stage. CE81T cells expressed IL-19 and its receptors. IL-19 induced phosphorylation of STAT3, P38, JNK, ERK1/2, Akt, and NF-κB in CE81T cells. IL-19 promoted the proliferation, colonization, and migration of CE81T cells, which were antagonized by 1BB1 and 51D. IL-19 also induced expression of the transcripts of TGF-β, cyclin B1, CXCR4, and MMP-1 in CE81T cells. In CE81T tumor-bearing mice, 1BB1 reduced tumor growth and downregulated TGF-β, cyclin B1, MMP-1, and CXCR4 expression in tumors.Conclusions/Significance:IL-19 affects the pathogenesis of esophageal cancer. IL-19 mAb (1BB1) is potentially a potent drug for esophageal cancer therapy.

Original languageEnglish
Article numbere75254
JournalPLoS One
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 9 2013

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Interleukins
squamous cell carcinoma
interleukins
Tumors
esophageal neoplasms
Esophageal Neoplasms
neoplasms
interstitial collagenase
Cyclin B1
cyclins
Neoplasms
Matrix Metalloproteinases
Bearings (structural)
receptors
Phosphorylation
SCID Mice
mice
cells
Growth
cell movement

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Inhibiting Interleukin-19 Activity Ameliorates Esophageal Squamous Cell Carcinoma Progression. / Hsing, Chung-Hsi; Kwok, Franky Antonius; Cheng, Hung Chi; Li, Chien Feng; Chang, Ming Shi.

In: PLoS One, Vol. 8, No. 10, e75254, 09.10.2013.

Research output: Contribution to journalArticle

Hsing, Chung-Hsi ; Kwok, Franky Antonius ; Cheng, Hung Chi ; Li, Chien Feng ; Chang, Ming Shi. / Inhibiting Interleukin-19 Activity Ameliorates Esophageal Squamous Cell Carcinoma Progression. In: PLoS One. 2013 ; Vol. 8, No. 10.
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abstract = "Background:IL-19 is expressed in esophageal squamous cell carcinoma (SCC), but its biological effect on esophageal cancer remains unclear. We determined the correlation between IL-19 expression levels and clinicopathological variables and explored the effects of IL-19 on the esophageal SCC in vivo and in vitro.Methodology/Principal Findings:We determined the expression levels of esophageal SCC tissues from 60 patients using immunohistochemistry. We examined the effects of IL-19 on intracellular signaling, cytokines production as well as proliferation, colonization, and migration in the human esophageal SCC cell line CE81T. Monoclonal antibodies (mAbs) against IL-19 (1BB1) and its receptor IL-20R1 (51D) were used to antagonize the effects of IL-19. We injected SCID mice with CE81T cells and then treated them with anti-IL-19 mAb or control IgG every 3 days and determined tumor growth for 32 days. Of the 60 esophageal SCC patients, 36 patients (60{\%}) were IL-19 strongly stained, which was associated with advanced tumor stage. CE81T cells expressed IL-19 and its receptors. IL-19 induced phosphorylation of STAT3, P38, JNK, ERK1/2, Akt, and NF-κB in CE81T cells. IL-19 promoted the proliferation, colonization, and migration of CE81T cells, which were antagonized by 1BB1 and 51D. IL-19 also induced expression of the transcripts of TGF-β, cyclin B1, CXCR4, and MMP-1 in CE81T cells. In CE81T tumor-bearing mice, 1BB1 reduced tumor growth and downregulated TGF-β, cyclin B1, MMP-1, and CXCR4 expression in tumors.Conclusions/Significance:IL-19 affects the pathogenesis of esophageal cancer. IL-19 mAb (1BB1) is potentially a potent drug for esophageal cancer therapy.",
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AB - Background:IL-19 is expressed in esophageal squamous cell carcinoma (SCC), but its biological effect on esophageal cancer remains unclear. We determined the correlation between IL-19 expression levels and clinicopathological variables and explored the effects of IL-19 on the esophageal SCC in vivo and in vitro.Methodology/Principal Findings:We determined the expression levels of esophageal SCC tissues from 60 patients using immunohistochemistry. We examined the effects of IL-19 on intracellular signaling, cytokines production as well as proliferation, colonization, and migration in the human esophageal SCC cell line CE81T. Monoclonal antibodies (mAbs) against IL-19 (1BB1) and its receptor IL-20R1 (51D) were used to antagonize the effects of IL-19. We injected SCID mice with CE81T cells and then treated them with anti-IL-19 mAb or control IgG every 3 days and determined tumor growth for 32 days. Of the 60 esophageal SCC patients, 36 patients (60%) were IL-19 strongly stained, which was associated with advanced tumor stage. CE81T cells expressed IL-19 and its receptors. IL-19 induced phosphorylation of STAT3, P38, JNK, ERK1/2, Akt, and NF-κB in CE81T cells. IL-19 promoted the proliferation, colonization, and migration of CE81T cells, which were antagonized by 1BB1 and 51D. IL-19 also induced expression of the transcripts of TGF-β, cyclin B1, CXCR4, and MMP-1 in CE81T cells. In CE81T tumor-bearing mice, 1BB1 reduced tumor growth and downregulated TGF-β, cyclin B1, MMP-1, and CXCR4 expression in tumors.Conclusions/Significance:IL-19 affects the pathogenesis of esophageal cancer. IL-19 mAb (1BB1) is potentially a potent drug for esophageal cancer therapy.

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