Recombinant viral protein VP1 suppresses HER-2 expression and migration/metastasis of breast cancer

Shao Wen Hung, Ching Feng Chiu, Tai An Chen, Chiao Li Chu, Chi Chang Huang, Lie Fen Shyur, Chi Ming Liang, Shu Mei Liang

研究成果: 雜誌貢獻文章

4 引文 (Scopus)

摘要

Breast cancer is one of the most common cancers in women worldwide and metastasis is the major cause of breast cancer death. Development of new therapeutic agents for inhibiting breast cancer metastasis is therefore an urgent need. We previously demonstrated that recombinant DNA-derived viral capsid protein VP1 (rVP1) of foot-and-mouth disease virus-induced apoptosis of MCF-7 breast cancer cells in vitro. Here, we investigated whether rVP1 exhibits any inhibitory effects on migration/metastasis and human epidermal growth factor receptor 2 (HER-2), a well-known biomarker for poor prognosis of breast cancer. The effects of rVP1 on cancer cell migration/invasion and metastasis were evaluated using Transwell migration assay and animal cancer models of metastasis. Western blotting, RT-PCR, flow cytometry, immunohistochemistry, and immunofluorescence staining techniques were used to investigate the effects of rVP1 on HER-2 and signal transduction mediators. Non-cytotoxic concentrations of rVP1-induced mesenchymal-epithelial transition and significantly suppressed AP-2α and HER-2 expression as well as the migration and invasion of a variety of breast cancer cell lines in a β1-integrin-dependent manner in vitro. Gross and histopathologic examinations showed that rVP1 also suppressed metastasis of several breast cancer cell lines, including HER-2-overexpressing SK-BR-3 and BT-474 cells to lung, liver, or peripheral lymph node in orthotopic allograft/xenograft murine models. In addition, rVP1 significantly prolonged survival in breast cancer-bearing mice. Notably, no apparent side effects of rVP1 were detected, as shown by normal complete blood count levels and serum biochemistry profiles, including AST, ALT, BUN, and creatine. This study demonstrates that rVP1 suppresses the migration, invasion, and metastasis of breast cancer cells via binding to β1 integrin receptor and down-regulation of AP-2α and HER-2 expression. The effectiveness of rVP1 on inhibiting migration/metastasis of breast cancer and HER-2 expression suggests that it may be suitable for serving as potential therapeutics for metastatic breast cancer particularly HER-2-overexpressing cancer.
原文英語
頁(從 - 到)89-105
頁數17
期刊Breast Cancer Research and Treatment
136
發行號1
DOIs
出版狀態已發佈 - 十一月 1 2012
對外發佈Yes

指紋

Viral Proteins
Recombinant Proteins
Breast Neoplasms
Neoplasm Metastasis
Integrins
Neoplasms
human ERBB2 protein
Foot-and-Mouth Disease Virus
Cell Line
Epithelial-Mesenchymal Transition
Recombinant DNA
Blood Cell Count
Creatine
Blood Urea Nitrogen
Capsid Proteins
Heterografts
Biochemistry
Cell Movement
Fluorescent Antibody Technique
Allografts

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

Recombinant viral protein VP1 suppresses HER-2 expression and migration/metastasis of breast cancer. / Hung, Shao Wen; Chiu, Ching Feng; Chen, Tai An; Chu, Chiao Li; Huang, Chi Chang; Shyur, Lie Fen; Liang, Chi Ming; Liang, Shu Mei.

於: Breast Cancer Research and Treatment, 卷 136, 編號 1, 01.11.2012, p. 89-105.

研究成果: 雜誌貢獻文章

Hung, Shao Wen ; Chiu, Ching Feng ; Chen, Tai An ; Chu, Chiao Li ; Huang, Chi Chang ; Shyur, Lie Fen ; Liang, Chi Ming ; Liang, Shu Mei. / Recombinant viral protein VP1 suppresses HER-2 expression and migration/metastasis of breast cancer. 於: Breast Cancer Research and Treatment. 2012 ; 卷 136, 編號 1. 頁 89-105.
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AU - Hung, Shao Wen

AU - Chiu, Ching Feng

AU - Chen, Tai An

AU - Chu, Chiao Li

AU - Huang, Chi Chang

AU - Shyur, Lie Fen

AU - Liang, Chi Ming

AU - Liang, Shu Mei

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N2 - Breast cancer is one of the most common cancers in women worldwide and metastasis is the major cause of breast cancer death. Development of new therapeutic agents for inhibiting breast cancer metastasis is therefore an urgent need. We previously demonstrated that recombinant DNA-derived viral capsid protein VP1 (rVP1) of foot-and-mouth disease virus-induced apoptosis of MCF-7 breast cancer cells in vitro. Here, we investigated whether rVP1 exhibits any inhibitory effects on migration/metastasis and human epidermal growth factor receptor 2 (HER-2), a well-known biomarker for poor prognosis of breast cancer. The effects of rVP1 on cancer cell migration/invasion and metastasis were evaluated using Transwell migration assay and animal cancer models of metastasis. Western blotting, RT-PCR, flow cytometry, immunohistochemistry, and immunofluorescence staining techniques were used to investigate the effects of rVP1 on HER-2 and signal transduction mediators. Non-cytotoxic concentrations of rVP1-induced mesenchymal-epithelial transition and significantly suppressed AP-2α and HER-2 expression as well as the migration and invasion of a variety of breast cancer cell lines in a β1-integrin-dependent manner in vitro. Gross and histopathologic examinations showed that rVP1 also suppressed metastasis of several breast cancer cell lines, including HER-2-overexpressing SK-BR-3 and BT-474 cells to lung, liver, or peripheral lymph node in orthotopic allograft/xenograft murine models. In addition, rVP1 significantly prolonged survival in breast cancer-bearing mice. Notably, no apparent side effects of rVP1 were detected, as shown by normal complete blood count levels and serum biochemistry profiles, including AST, ALT, BUN, and creatine. This study demonstrates that rVP1 suppresses the migration, invasion, and metastasis of breast cancer cells via binding to β1 integrin receptor and down-regulation of AP-2α and HER-2 expression. The effectiveness of rVP1 on inhibiting migration/metastasis of breast cancer and HER-2 expression suggests that it may be suitable for serving as potential therapeutics for metastatic breast cancer particularly HER-2-overexpressing cancer.

AB - Breast cancer is one of the most common cancers in women worldwide and metastasis is the major cause of breast cancer death. Development of new therapeutic agents for inhibiting breast cancer metastasis is therefore an urgent need. We previously demonstrated that recombinant DNA-derived viral capsid protein VP1 (rVP1) of foot-and-mouth disease virus-induced apoptosis of MCF-7 breast cancer cells in vitro. Here, we investigated whether rVP1 exhibits any inhibitory effects on migration/metastasis and human epidermal growth factor receptor 2 (HER-2), a well-known biomarker for poor prognosis of breast cancer. The effects of rVP1 on cancer cell migration/invasion and metastasis were evaluated using Transwell migration assay and animal cancer models of metastasis. Western blotting, RT-PCR, flow cytometry, immunohistochemistry, and immunofluorescence staining techniques were used to investigate the effects of rVP1 on HER-2 and signal transduction mediators. Non-cytotoxic concentrations of rVP1-induced mesenchymal-epithelial transition and significantly suppressed AP-2α and HER-2 expression as well as the migration and invasion of a variety of breast cancer cell lines in a β1-integrin-dependent manner in vitro. Gross and histopathologic examinations showed that rVP1 also suppressed metastasis of several breast cancer cell lines, including HER-2-overexpressing SK-BR-3 and BT-474 cells to lung, liver, or peripheral lymph node in orthotopic allograft/xenograft murine models. In addition, rVP1 significantly prolonged survival in breast cancer-bearing mice. Notably, no apparent side effects of rVP1 were detected, as shown by normal complete blood count levels and serum biochemistry profiles, including AST, ALT, BUN, and creatine. This study demonstrates that rVP1 suppresses the migration, invasion, and metastasis of breast cancer cells via binding to β1 integrin receptor and down-regulation of AP-2α and HER-2 expression. The effectiveness of rVP1 on inhibiting migration/metastasis of breast cancer and HER-2 expression suggests that it may be suitable for serving as potential therapeutics for metastatic breast cancer particularly HER-2-overexpressing cancer.

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