Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models

Yu Hsiang Hsu, Chung-Hsi Hsing, Chien Feng Li, Chien Hui Chan, Ming Chung Chang, Jing Jou Yan, Ming Shi Chang

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

IL-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about its role in breast cancer. We explored the function of IL-20 in tumor growth and metastasis, as well as in clinical outcome. Tumor expression of IL-20 was assessed by immunohistochemical staining among 198 patients with invasive ductal carcinoma of the breast, using available clinical and survival data. IL-20 expression was associated with advanced tumor stage, greater tumor metastasis, and worse survival. Reverse transcription quantitative polymerase chain reaction showed that clinical breast tumor tissue expressed higher levels of IL-20 and its receptors than did nontumorous breast tissue. IL-20 was also highly expressed in breast cancer bone-metastasis tissue. In vitro, IL-20 upregulated matrix metalloproteinase-9, matrix metalloproteinase-12, cathepsin K, and cathepsin G, and enhanced proliferation and migration of breast cancer cells, which were inhibited by anti-IL-20 mAb 7E. In vivo, we generated murine models to evaluate the therapeutic potential of 7E, using luminescence intensity, radiological scans, and micro-computed tomography. 7E reduced tumor growth, suppressed bone colonization, diminished tumor-mediated osteolysis, and lessened bone density decrement in mice injected with breast cancer cells. In conclusion, our results suggest that IL-20 plays pivotal roles in the tumor progression of breast cancer. IL-20 expression in breast cancer tissue is associated with a poor clinical outcome. Anti-IL-20 mAb 7E suppressed bone colonization and decreased osteolytic bone lesions. Therefore, IL-20 may be a novel target in treating breast tumor-induced osteolysis.

Original languageEnglish
Pages (from-to)1981-1991
Number of pages11
JournalJournal of Immunology
Volume188
Issue number4
DOIs
Publication statusPublished - Feb 15 2012
Externally publishedYes

Fingerprint

Bone Neoplasms
Osteolysis
Monoclonal Antibodies
Breast Neoplasms
Neoplasms
Neoplasm Metastasis
Bone and Bones
interleukin 20
Matrix Metalloproteinase 12
Cathepsin K
Cathepsin G
Carcinoma, Ductal, Breast
Survival
Bone Development
Matrix Metalloproteinase 9
Luminescence
Bone Density
Reverse Transcription
Rheumatoid Arthritis
Atherosclerosis

ASJC Scopus subject areas

  • Immunology

Cite this

Hsu, Y. H., Hsing, C-H., Li, C. F., Chan, C. H., Chang, M. C., Yan, J. J., & Chang, M. S. (2012). Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models. Journal of Immunology, 188(4), 1981-1991. https://doi.org/10.4049/jimmunol.1102843

Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models. / Hsu, Yu Hsiang; Hsing, Chung-Hsi; Li, Chien Feng; Chan, Chien Hui; Chang, Ming Chung; Yan, Jing Jou; Chang, Ming Shi.

In: Journal of Immunology, Vol. 188, No. 4, 15.02.2012, p. 1981-1991.

Research output: Contribution to journalArticle

Hsu, YH, Hsing, C-H, Li, CF, Chan, CH, Chang, MC, Yan, JJ & Chang, MS 2012, 'Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models', Journal of Immunology, vol. 188, no. 4, pp. 1981-1991. https://doi.org/10.4049/jimmunol.1102843
Hsu, Yu Hsiang ; Hsing, Chung-Hsi ; Li, Chien Feng ; Chan, Chien Hui ; Chang, Ming Chung ; Yan, Jing Jou ; Chang, Ming Shi. / Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models. In: Journal of Immunology. 2012 ; Vol. 188, No. 4. pp. 1981-1991.
@article{3e5db1d440ce4302b6c6c09d1dab21b6,
title = "Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models",
abstract = "IL-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about its role in breast cancer. We explored the function of IL-20 in tumor growth and metastasis, as well as in clinical outcome. Tumor expression of IL-20 was assessed by immunohistochemical staining among 198 patients with invasive ductal carcinoma of the breast, using available clinical and survival data. IL-20 expression was associated with advanced tumor stage, greater tumor metastasis, and worse survival. Reverse transcription quantitative polymerase chain reaction showed that clinical breast tumor tissue expressed higher levels of IL-20 and its receptors than did nontumorous breast tissue. IL-20 was also highly expressed in breast cancer bone-metastasis tissue. In vitro, IL-20 upregulated matrix metalloproteinase-9, matrix metalloproteinase-12, cathepsin K, and cathepsin G, and enhanced proliferation and migration of breast cancer cells, which were inhibited by anti-IL-20 mAb 7E. In vivo, we generated murine models to evaluate the therapeutic potential of 7E, using luminescence intensity, radiological scans, and micro-computed tomography. 7E reduced tumor growth, suppressed bone colonization, diminished tumor-mediated osteolysis, and lessened bone density decrement in mice injected with breast cancer cells. In conclusion, our results suggest that IL-20 plays pivotal roles in the tumor progression of breast cancer. IL-20 expression in breast cancer tissue is associated with a poor clinical outcome. Anti-IL-20 mAb 7E suppressed bone colonization and decreased osteolytic bone lesions. Therefore, IL-20 may be a novel target in treating breast tumor-induced osteolysis.",
author = "Hsu, {Yu Hsiang} and Chung-Hsi Hsing and Li, {Chien Feng} and Chan, {Chien Hui} and Chang, {Ming Chung} and Yan, {Jing Jou} and Chang, {Ming Shi}",
year = "2012",
month = "2",
day = "15",
doi = "10.4049/jimmunol.1102843",
language = "English",
volume = "188",
pages = "1981--1991",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models

AU - Hsu, Yu Hsiang

AU - Hsing, Chung-Hsi

AU - Li, Chien Feng

AU - Chan, Chien Hui

AU - Chang, Ming Chung

AU - Yan, Jing Jou

AU - Chang, Ming Shi

PY - 2012/2/15

Y1 - 2012/2/15

N2 - IL-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about its role in breast cancer. We explored the function of IL-20 in tumor growth and metastasis, as well as in clinical outcome. Tumor expression of IL-20 was assessed by immunohistochemical staining among 198 patients with invasive ductal carcinoma of the breast, using available clinical and survival data. IL-20 expression was associated with advanced tumor stage, greater tumor metastasis, and worse survival. Reverse transcription quantitative polymerase chain reaction showed that clinical breast tumor tissue expressed higher levels of IL-20 and its receptors than did nontumorous breast tissue. IL-20 was also highly expressed in breast cancer bone-metastasis tissue. In vitro, IL-20 upregulated matrix metalloproteinase-9, matrix metalloproteinase-12, cathepsin K, and cathepsin G, and enhanced proliferation and migration of breast cancer cells, which were inhibited by anti-IL-20 mAb 7E. In vivo, we generated murine models to evaluate the therapeutic potential of 7E, using luminescence intensity, radiological scans, and micro-computed tomography. 7E reduced tumor growth, suppressed bone colonization, diminished tumor-mediated osteolysis, and lessened bone density decrement in mice injected with breast cancer cells. In conclusion, our results suggest that IL-20 plays pivotal roles in the tumor progression of breast cancer. IL-20 expression in breast cancer tissue is associated with a poor clinical outcome. Anti-IL-20 mAb 7E suppressed bone colonization and decreased osteolytic bone lesions. Therefore, IL-20 may be a novel target in treating breast tumor-induced osteolysis.

AB - IL-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about its role in breast cancer. We explored the function of IL-20 in tumor growth and metastasis, as well as in clinical outcome. Tumor expression of IL-20 was assessed by immunohistochemical staining among 198 patients with invasive ductal carcinoma of the breast, using available clinical and survival data. IL-20 expression was associated with advanced tumor stage, greater tumor metastasis, and worse survival. Reverse transcription quantitative polymerase chain reaction showed that clinical breast tumor tissue expressed higher levels of IL-20 and its receptors than did nontumorous breast tissue. IL-20 was also highly expressed in breast cancer bone-metastasis tissue. In vitro, IL-20 upregulated matrix metalloproteinase-9, matrix metalloproteinase-12, cathepsin K, and cathepsin G, and enhanced proliferation and migration of breast cancer cells, which were inhibited by anti-IL-20 mAb 7E. In vivo, we generated murine models to evaluate the therapeutic potential of 7E, using luminescence intensity, radiological scans, and micro-computed tomography. 7E reduced tumor growth, suppressed bone colonization, diminished tumor-mediated osteolysis, and lessened bone density decrement in mice injected with breast cancer cells. In conclusion, our results suggest that IL-20 plays pivotal roles in the tumor progression of breast cancer. IL-20 expression in breast cancer tissue is associated with a poor clinical outcome. Anti-IL-20 mAb 7E suppressed bone colonization and decreased osteolytic bone lesions. Therefore, IL-20 may be a novel target in treating breast tumor-induced osteolysis.

UR - http://www.scopus.com/inward/record.url?scp=84863165532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863165532&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1102843

DO - 10.4049/jimmunol.1102843

M3 - Article

VL - 188

SP - 1981

EP - 1991

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -