Upregulated IL-19 in breast cancer promotes tumor progression and affects clinical outcome

Chung-Hsi Hsing, Hung Chi Cheng, Yu Hsiang Hsu, Chien Hui Chan, Ching Hua Yeh, Chien Feng Li, Ming Shi Chang

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Purpose: Interleukin (IL)-19 was expressed in invasive ductal carcinoma (IDC) of the breast tissue but not in healthy breast tissue. We explored the effects of IL-19 on the pathogenesis of breast cancer and its clinical outcome. Experimental Design: Tumor expression of IL-19 was assessed by immunohistochemistry and/or real-time quantitative PCR between two groups of patients with breast IDC (n = 60 and 143, respectively) with available clinical and survival data. We examined the effects of IL-19 on cytokine and chemokine production as well as proliferation and migration in breast cancer cells. Mice were injected with IL-19-overexpressing or vector control 67NR cells and the tumor growth and lung metastatic micronodules were measured. Results: Of the IDC specimens, high IL-19 expression was associated with advanced tumor stage, high tumor metastasis, and worse survival. In vitro, IL-19 induced transcripts of IL-1β, IL-6, TGF-β, matrix metalloproteinase (MMP)2, MMP9, and CXCR4 in 4T1 breast cancer cells; induced fibronectin expression and assembly; and promoted cancer cell proliferation and migration, which were inhibited by anti-IL-19 monoclonal antibody (mAb). Endogenous fibronectin expression and cancer cell migration were lower in IL-19 knockdown 4T1 cells. In 4T1 cells, hypoxia induced IL-19 and CXCR4 expression, which was inhibited by anti-IL-19 mAb. IL-19 overexpression in noninvasive 67NR cancer cells increased cell proliferation and migration. In vivo, mice injected with IL-19-overexpressing 67NR cell clones showed larger tumors and more metastatic micronodules in the lung. Conclusions: High IL-19 expression in breast cancer tissue is associated with a poor clinical outcome. IL-19 is pivotal in the pathogenesis of breast cancer.

Original languageEnglish
Pages (from-to)713-725
Number of pages13
JournalClinical Cancer Research
Volume18
Issue number3
DOIs
Publication statusPublished - Feb 1 2012

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Interleukins
Breast Neoplasms
Neoplasms
Cell Movement
Carcinoma, Ductal, Breast
Fibronectins
Monoclonal Antibodies
Cell Proliferation
Cell Hypoxia
Lung
Ductal Carcinoma
Survival
Matrix Metalloproteinase 2
Interleukin-1
Chemokines
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hsing, C-H., Cheng, H. C., Hsu, Y. H., Chan, C. H., Yeh, C. H., Li, C. F., & Chang, M. S. (2012). Upregulated IL-19 in breast cancer promotes tumor progression and affects clinical outcome. Clinical Cancer Research, 18(3), 713-725. https://doi.org/10.1158/1078-0432.CCR-11-1532

Upregulated IL-19 in breast cancer promotes tumor progression and affects clinical outcome. / Hsing, Chung-Hsi; Cheng, Hung Chi; Hsu, Yu Hsiang; Chan, Chien Hui; Yeh, Ching Hua; Li, Chien Feng; Chang, Ming Shi.

In: Clinical Cancer Research, Vol. 18, No. 3, 01.02.2012, p. 713-725.

Research output: Contribution to journalArticle

Hsing, C-H, Cheng, HC, Hsu, YH, Chan, CH, Yeh, CH, Li, CF & Chang, MS 2012, 'Upregulated IL-19 in breast cancer promotes tumor progression and affects clinical outcome', Clinical Cancer Research, vol. 18, no. 3, pp. 713-725. https://doi.org/10.1158/1078-0432.CCR-11-1532
Hsing, Chung-Hsi ; Cheng, Hung Chi ; Hsu, Yu Hsiang ; Chan, Chien Hui ; Yeh, Ching Hua ; Li, Chien Feng ; Chang, Ming Shi. / Upregulated IL-19 in breast cancer promotes tumor progression and affects clinical outcome. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 3. pp. 713-725.
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AU - Yeh, Ching Hua

AU - Li, Chien Feng

AU - Chang, Ming Shi

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AB - Purpose: Interleukin (IL)-19 was expressed in invasive ductal carcinoma (IDC) of the breast tissue but not in healthy breast tissue. We explored the effects of IL-19 on the pathogenesis of breast cancer and its clinical outcome. Experimental Design: Tumor expression of IL-19 was assessed by immunohistochemistry and/or real-time quantitative PCR between two groups of patients with breast IDC (n = 60 and 143, respectively) with available clinical and survival data. We examined the effects of IL-19 on cytokine and chemokine production as well as proliferation and migration in breast cancer cells. Mice were injected with IL-19-overexpressing or vector control 67NR cells and the tumor growth and lung metastatic micronodules were measured. Results: Of the IDC specimens, high IL-19 expression was associated with advanced tumor stage, high tumor metastasis, and worse survival. In vitro, IL-19 induced transcripts of IL-1β, IL-6, TGF-β, matrix metalloproteinase (MMP)2, MMP9, and CXCR4 in 4T1 breast cancer cells; induced fibronectin expression and assembly; and promoted cancer cell proliferation and migration, which were inhibited by anti-IL-19 monoclonal antibody (mAb). Endogenous fibronectin expression and cancer cell migration were lower in IL-19 knockdown 4T1 cells. In 4T1 cells, hypoxia induced IL-19 and CXCR4 expression, which was inhibited by anti-IL-19 mAb. IL-19 overexpression in noninvasive 67NR cancer cells increased cell proliferation and migration. In vivo, mice injected with IL-19-overexpressing 67NR cell clones showed larger tumors and more metastatic micronodules in the lung. Conclusions: High IL-19 expression in breast cancer tissue is associated with a poor clinical outcome. IL-19 is pivotal in the pathogenesis of breast cancer.

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