Introduction of Androgen Receptor Targeting shRNA Inhibits Tumor Growth in Patient-Derived Prostate Cancer Xenografts
Patient-derived xenograft (PDX) models have been established as important preclinical cancer models, overcoming some of the limitations associated with the use of cancer cell lines. The utility of prostate cancer PDX models has been limited by an inability to genetically manipulate them in vivo and...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/30/11/683 |
| _version_ | 1827640118841704448 |
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| author | Patrick B. Thomas Saeid Alinezhad Andre Joshi Katrina Sweeney Brian W. C. Tse Gregor Tevz Stephen McPherson Colleen C. Nelson Elizabeth D. Williams Ian Vela |
| author_facet | Patrick B. Thomas Saeid Alinezhad Andre Joshi Katrina Sweeney Brian W. C. Tse Gregor Tevz Stephen McPherson Colleen C. Nelson Elizabeth D. Williams Ian Vela |
| author_sort | Patrick B. Thomas |
| collection | DOAJ |
| description | Patient-derived xenograft (PDX) models have been established as important preclinical cancer models, overcoming some of the limitations associated with the use of cancer cell lines. The utility of prostate cancer PDX models has been limited by an inability to genetically manipulate them in vivo and difficulties sustaining PDX-derived cancer cells in culture. Viable, short-term propagation of PDX models would allow in vitro transfection with traceable reporters or manipulation of gene expression relevant to different studies within the prostate cancer field. Here, we report an organoid culture system that supports the growth of prostate cancer PDX cells in vitro and permits genetic manipulation, substantially increasing the scope to use PDXs to study the pathobiology of prostate cancer and define potential therapeutic targets. We have established a short-term PDX-derived in vitro cell culture system which enables genetic manipulation of prostate cancer PDXs LuCaP35 and BM18. Genetically manipulated cells could be re-established as viable xenografts when re-implanted subcutaneously in immunocompromised mice and were able to be serially passaged. Tumor growth of the androgen-dependent LuCaP35 PDX was significantly inhibited following depletion of the androgen receptor (AR) in vivo. Taken together, this system provides a method to generate novel preclinical models to assess the impact of controlled genetic perturbations and allows for targeting specific genes of interest in the complex biological setting of solid tumors. |
| first_indexed | 2024-03-09T16:54:29Z |
| format | Article |
| id | doaj.art-21c1299ac58a487cb97e5ad972e9f1c4 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-09T16:54:29Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-21c1299ac58a487cb97e5ad972e9f1c42023-11-24T14:37:01ZengMDPI AGCurrent Oncology1198-00521718-77292023-10-0130119437944710.3390/curroncol30110683Introduction of Androgen Receptor Targeting shRNA Inhibits Tumor Growth in Patient-Derived Prostate Cancer XenograftsPatrick B. Thomas0Saeid Alinezhad1Andre Joshi2Katrina Sweeney3Brian W. C. Tse4Gregor Tevz5Stephen McPherson6Colleen C. Nelson7Elizabeth D. Williams8Ian Vela9School of Biomedical Sciences at Translational Research Institute (TRI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4102, AustraliaSchool of Biomedical Sciences at Translational Research Institute (TRI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4102, AustraliaSchool of Biomedical Sciences at Translational Research Institute (TRI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4102, AustraliaSchool of Biomedical Sciences at Translational Research Institute (TRI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4102, AustraliaPreclinical Imaging Facility, Translational Research Institute (TRI), Brisbane, QLD 4102, AustraliaSchool of Biomedical Sciences at Translational Research Institute (TRI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4102, AustraliaSchool of Biomedical Sciences at Translational Research Institute (TRI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4102, AustraliaSchool of Biomedical Sciences at Translational Research Institute (TRI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4102, AustraliaSchool of Biomedical Sciences at Translational Research Institute (TRI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4102, AustraliaSchool of Biomedical Sciences at Translational Research Institute (TRI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, QLD 4102, AustraliaPatient-derived xenograft (PDX) models have been established as important preclinical cancer models, overcoming some of the limitations associated with the use of cancer cell lines. The utility of prostate cancer PDX models has been limited by an inability to genetically manipulate them in vivo and difficulties sustaining PDX-derived cancer cells in culture. Viable, short-term propagation of PDX models would allow in vitro transfection with traceable reporters or manipulation of gene expression relevant to different studies within the prostate cancer field. Here, we report an organoid culture system that supports the growth of prostate cancer PDX cells in vitro and permits genetic manipulation, substantially increasing the scope to use PDXs to study the pathobiology of prostate cancer and define potential therapeutic targets. We have established a short-term PDX-derived in vitro cell culture system which enables genetic manipulation of prostate cancer PDXs LuCaP35 and BM18. Genetically manipulated cells could be re-established as viable xenografts when re-implanted subcutaneously in immunocompromised mice and were able to be serially passaged. Tumor growth of the androgen-dependent LuCaP35 PDX was significantly inhibited following depletion of the androgen receptor (AR) in vivo. Taken together, this system provides a method to generate novel preclinical models to assess the impact of controlled genetic perturbations and allows for targeting specific genes of interest in the complex biological setting of solid tumors.https://www.mdpi.com/1718-7729/30/11/683prostate cancerorganoidsprecision medicinepatient-derived xenograftandrogen receptor |
| spellingShingle | Patrick B. Thomas Saeid Alinezhad Andre Joshi Katrina Sweeney Brian W. C. Tse Gregor Tevz Stephen McPherson Colleen C. Nelson Elizabeth D. Williams Ian Vela Introduction of Androgen Receptor Targeting shRNA Inhibits Tumor Growth in Patient-Derived Prostate Cancer Xenografts Current Oncology prostate cancer organoids precision medicine patient-derived xenograft androgen receptor |
| title | Introduction of Androgen Receptor Targeting shRNA Inhibits Tumor Growth in Patient-Derived Prostate Cancer Xenografts |
| title_full | Introduction of Androgen Receptor Targeting shRNA Inhibits Tumor Growth in Patient-Derived Prostate Cancer Xenografts |
| title_fullStr | Introduction of Androgen Receptor Targeting shRNA Inhibits Tumor Growth in Patient-Derived Prostate Cancer Xenografts |
| title_full_unstemmed | Introduction of Androgen Receptor Targeting shRNA Inhibits Tumor Growth in Patient-Derived Prostate Cancer Xenografts |
| title_short | Introduction of Androgen Receptor Targeting shRNA Inhibits Tumor Growth in Patient-Derived Prostate Cancer Xenografts |
| title_sort | introduction of androgen receptor targeting shrna inhibits tumor growth in patient derived prostate cancer xenografts |
| topic | prostate cancer organoids precision medicine patient-derived xenograft androgen receptor |
| url | https://www.mdpi.com/1718-7729/30/11/683 |
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