KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer
Recent reports have suggested the role of kallikrein-related peptidase 4 (KLK4) to be that of remodeling the tumor microenvironment in many cancers, including prostate cancer. Notably, these studies have suggested a pro-tumorigenic role for KLK4, especially in prostate cancer. However, these have be...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/12/3501 |
| _version_ | 1797546884849467392 |
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| author | Brian W.-C. Tse Thomas Kryza Mei-Chun Yeh Ying Dong Kamil A. Sokolowski Carina Walpole Tobias Dreyer Johanna Felber Jonathan Harris Viktor Magdolen Pamela J. Russell Judith A. Clements |
| author_facet | Brian W.-C. Tse Thomas Kryza Mei-Chun Yeh Ying Dong Kamil A. Sokolowski Carina Walpole Tobias Dreyer Johanna Felber Jonathan Harris Viktor Magdolen Pamela J. Russell Judith A. Clements |
| author_sort | Brian W.-C. Tse |
| collection | DOAJ |
| description | Recent reports have suggested the role of kallikrein-related peptidase 4 (KLK4) to be that of remodeling the tumor microenvironment in many cancers, including prostate cancer. Notably, these studies have suggested a pro-tumorigenic role for KLK4, especially in prostate cancer. However, these have been primarily in vitro studies, with limited in vivo studies performed to date. Herein, we employed an orthotopic inoculation xenograft model to mimic the growth of primary tumors, and an intracardiac injection to induce metastatic dissemination to determine the in vivo tumorigenic effects of KLK4 overexpressed in PC3 prostate cancer cells. Notably, we found that these KLK4-expressing cells gave rise to smaller localized tumors and decreased metastases than the parent PC-3 cells. To our knowledge, this is the first report of an anti-tumorigenic effect of KLK4, particularly in prostate cancer. These findings also provide a cautionary tale of the need for in vivo analyses to substantiate in vitro experimental data. |
| first_indexed | 2024-03-10T14:35:33Z |
| format | Article |
| id | doaj.art-06cfdc21564a42d093a287b2b159d513 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T14:35:33Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-06cfdc21564a42d093a287b2b159d5132023-11-20T22:11:02ZengMDPI AGCancers2072-66942020-11-011212350110.3390/cancers12123501KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate CancerBrian W.-C. Tse0Thomas Kryza1Mei-Chun Yeh2Ying Dong3Kamil A. Sokolowski4Carina Walpole5Tobias Dreyer6Johanna Felber7Jonathan Harris8Viktor Magdolen9Pamela J. Russell10Judith A. Clements11Preclinical Imaging Facility, Translational Research Institute, Brisbane, QLD 4102, AustraliaAustralian Prostate Cancer Research Centre—Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, QLD 4102, AustraliaAustralian Prostate Cancer Research Centre—Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, QLD 4102, AustraliaAustralian Prostate Cancer Research Centre—Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, QLD 4102, AustraliaPreclinical Imaging Facility, Translational Research Institute, Brisbane, QLD 4102, AustraliaAustralian Prostate Cancer Research Centre—Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, QLD 4102, AustraliaClinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, 81675 Munich, GermanyClinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, 81675 Munich, GermanySchool of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4102, AustraliaClinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, 81675 Munich, GermanyAustralian Prostate Cancer Research Centre—Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, QLD 4102, AustraliaAustralian Prostate Cancer Research Centre—Queensland, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, QLD 4102, AustraliaRecent reports have suggested the role of kallikrein-related peptidase 4 (KLK4) to be that of remodeling the tumor microenvironment in many cancers, including prostate cancer. Notably, these studies have suggested a pro-tumorigenic role for KLK4, especially in prostate cancer. However, these have been primarily in vitro studies, with limited in vivo studies performed to date. Herein, we employed an orthotopic inoculation xenograft model to mimic the growth of primary tumors, and an intracardiac injection to induce metastatic dissemination to determine the in vivo tumorigenic effects of KLK4 overexpressed in PC3 prostate cancer cells. Notably, we found that these KLK4-expressing cells gave rise to smaller localized tumors and decreased metastases than the parent PC-3 cells. To our knowledge, this is the first report of an anti-tumorigenic effect of KLK4, particularly in prostate cancer. These findings also provide a cautionary tale of the need for in vivo analyses to substantiate in vitro experimental data.https://www.mdpi.com/2072-6694/12/12/3501kallikrein-related peptidase 4KLK4prostate cancermetastasistumor xenograftsimaging |
| spellingShingle | Brian W.-C. Tse Thomas Kryza Mei-Chun Yeh Ying Dong Kamil A. Sokolowski Carina Walpole Tobias Dreyer Johanna Felber Jonathan Harris Viktor Magdolen Pamela J. Russell Judith A. Clements KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer Cancers kallikrein-related peptidase 4 KLK4 prostate cancer metastasis tumor xenografts imaging |
| title | KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer |
| title_full | KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer |
| title_fullStr | KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer |
| title_full_unstemmed | KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer |
| title_short | KLK4 Induces Anti-Tumor Effects in Human Xenograft Mouse Models of Orthotopic and Metastatic Prostate Cancer |
| title_sort | klk4 induces anti tumor effects in human xenograft mouse models of orthotopic and metastatic prostate cancer |
| topic | kallikrein-related peptidase 4 KLK4 prostate cancer metastasis tumor xenografts imaging |
| url | https://www.mdpi.com/2072-6694/12/12/3501 |
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