Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells
Cathepsin G is a serine protease secreted by activated neutrophils that play a role in the inflammatory response. Because neutrophils are known to be invading leukocytes in various tumors, their products may influence the characteristics of tumor cells such as the growth state, motility, and the adh...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2009-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2009/850940 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832552344792858624 |
|---|---|
| author | Tomoya Kudo Hideaki Kigoshi Takashi Hagiwara Takahisa Takino Masatoshi Yamazaki Satoru Yui |
| author_facet | Tomoya Kudo Hideaki Kigoshi Takashi Hagiwara Takahisa Takino Masatoshi Yamazaki Satoru Yui |
| author_sort | Tomoya Kudo |
| collection | DOAJ |
| description | Cathepsin G is a serine protease secreted by activated neutrophils that play a role in the inflammatory response. Because neutrophils are known to be invading leukocytes in various tumors, their products may influence the characteristics of tumor cells such as the growth state, motility, and the adhesiveness between cells or the extracellular matrix. Here, we demonstrate that cathepsin G induces cell-cell adhesion of MCF-7 human breast cancer cells resulting from the contact inhibition of cell movement on fibronectin but not on type IV collagen. Cathepsin G subsequently induced cell condensation, a very compact cell colony, resulting due to the increased strength of E-cadherin-mediated cell-cell adhesion. Cathepsin G action is protease activity-dependent and was inhibited by the presence of serine protease inhibitors. Cathepsin G promotes E-cadherin/catenin complex formation and Rap1 activation in MCF-7 cells, which reportedly regulates E-cadherin-based cell-cell junctions. Cathepsin G also promotes E-cadherin/protein kinase D1 (PKD1) complex formation, and Go6976, the selective PKD1 inhibitor, suppressed the cathepsin G-induced cell condensation. Our findings provide the first evidence that cathepsin G regulates E-cadherin function, suggesting that cathepsin G has a novel modulatory role against tumor cell-cell adhesion. |
| format | Article |
| id | doaj-art-288ea279ac8e4deb865cfcead2b1ff57 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-288ea279ac8e4deb865cfcead2b1ff572025-02-03T05:58:52ZengWileyMediators of Inflammation0962-93511466-18612009-01-01200910.1155/2009/850940850940Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer CellsTomoya Kudo0Hideaki Kigoshi1Takashi Hagiwara2Takahisa Takino3Masatoshi Yamazaki4Satoru Yui5Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko, Sagamihara, Kanagawa 229-0195, JapanFaculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko, Sagamihara, Kanagawa 229-0195, JapanFaculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko, Sagamihara, Kanagawa 229-0195, JapanDepartment of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, JapanFaculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko, Sagamihara, Kanagawa 229-0195, JapanFaculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Sagamiko, Sagamihara, Kanagawa 229-0195, JapanCathepsin G is a serine protease secreted by activated neutrophils that play a role in the inflammatory response. Because neutrophils are known to be invading leukocytes in various tumors, their products may influence the characteristics of tumor cells such as the growth state, motility, and the adhesiveness between cells or the extracellular matrix. Here, we demonstrate that cathepsin G induces cell-cell adhesion of MCF-7 human breast cancer cells resulting from the contact inhibition of cell movement on fibronectin but not on type IV collagen. Cathepsin G subsequently induced cell condensation, a very compact cell colony, resulting due to the increased strength of E-cadherin-mediated cell-cell adhesion. Cathepsin G action is protease activity-dependent and was inhibited by the presence of serine protease inhibitors. Cathepsin G promotes E-cadherin/catenin complex formation and Rap1 activation in MCF-7 cells, which reportedly regulates E-cadherin-based cell-cell junctions. Cathepsin G also promotes E-cadherin/protein kinase D1 (PKD1) complex formation, and Go6976, the selective PKD1 inhibitor, suppressed the cathepsin G-induced cell condensation. Our findings provide the first evidence that cathepsin G regulates E-cadherin function, suggesting that cathepsin G has a novel modulatory role against tumor cell-cell adhesion.http://dx.doi.org/10.1155/2009/850940 |
| spellingShingle | Tomoya Kudo Hideaki Kigoshi Takashi Hagiwara Takahisa Takino Masatoshi Yamazaki Satoru Yui Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells Mediators of Inflammation |
| title | Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells |
| title_full | Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells |
| title_fullStr | Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells |
| title_full_unstemmed | Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells |
| title_short | Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells |
| title_sort | cathepsin g a neutrophil protease induces compact cell cell adhesion in mcf 7 human breast cancer cells |
| url | http://dx.doi.org/10.1155/2009/850940 |
| work_keys_str_mv | AT tomoyakudo cathepsinganeutrophilproteaseinducescompactcellcelladhesioninmcf7humanbreastcancercells AT hideakikigoshi cathepsinganeutrophilproteaseinducescompactcellcelladhesioninmcf7humanbreastcancercells AT takashihagiwara cathepsinganeutrophilproteaseinducescompactcellcelladhesioninmcf7humanbreastcancercells AT takahisatakino cathepsinganeutrophilproteaseinducescompactcellcelladhesioninmcf7humanbreastcancercells AT masatoshiyamazaki cathepsinganeutrophilproteaseinducescompactcellcelladhesioninmcf7humanbreastcancercells AT satoruyui cathepsinganeutrophilproteaseinducescompactcellcelladhesioninmcf7humanbreastcancercells |