Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model
Abstract Globally, prostate cancer is the second most common malignancy in males, with over 400 thousand men dying from the disease each year. A common treatment modality for localized prostate cancer is radiotherapy. However, up to half of high-risk patients can relapse with radiorecurrent prostate...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-82546-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846101207405297664 |
|---|---|
| author | Gavin Frame Xiaoyong Huang Roni Haas Kabir A. Khan Hon S. Leong Thomas Kislinger Paul C. Boutros Michelle Downes Stanley K. Liu |
| author_facet | Gavin Frame Xiaoyong Huang Roni Haas Kabir A. Khan Hon S. Leong Thomas Kislinger Paul C. Boutros Michelle Downes Stanley K. Liu |
| author_sort | Gavin Frame |
| collection | DOAJ |
| description | Abstract Globally, prostate cancer is the second most common malignancy in males, with over 400 thousand men dying from the disease each year. A common treatment modality for localized prostate cancer is radiotherapy. However, up to half of high-risk patients can relapse with radiorecurrent prostate cancer, the aggressive clinical progression of which remains severely understudied. To address this, we have established an orthotopic mouse model for study that recapitulates the aggressive clinical progression of radiorecurrent prostate cancer. Radiorecurrent DU145 cells which survived conventional fraction (CF) irradiation were orthotopically injected into the prostates of athymic nude mice and monitored with bioluminescent imaging. CF tumours exhibited higher take rates and grew more rapidly than treatment-naïve parental tumours (PAR). Pathohistological analysis revealed extensive seminal vesicle invasion and necrosis in CF tumours, recapitulating the aggressive progression towards locally advanced disease exhibited by radiorecurrent tumours clinically. RNA sequencing of CF and PAR tumours identified ROBO1, CAV1, and CDH1 as candidate targets of radiorecurrent progression associated with biochemical relapse clinically. Together, this study presents a clinically relevant orthotopic model of radiorecurrent prostate cancer progression that will enable discovery of targets for therapeutic intervention to improve outcomes in prostate cancer patients. |
| format | Article |
| id | doaj-art-453f9fd37d3d4847bfd5e0e976e9ab5d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-453f9fd37d3d4847bfd5e0e976e9ab5d2024-12-29T12:24:21ZengNature PortfolioScientific Reports2045-23222024-12-0114111310.1038/s41598-024-82546-wAccelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse modelGavin Frame0Xiaoyong Huang1Roni Haas2Kabir A. Khan3Hon S. Leong4Thomas Kislinger5Paul C. Boutros6Michelle Downes7Stanley K. Liu8Department of Medical Biophysics, University of TorontoSunnybrook Research Institute, Sunnybrook Health Sciences CentreUniversity of California Los AngelesSunnybrook Research Institute, Sunnybrook Health Sciences CentreDepartment of Medical Biophysics, University of TorontoDepartment of Medical Biophysics, University of TorontoDepartment of Medical Biophysics, University of TorontoDivision of Anatomic Pathology, Precision Diagnostics & Therapeutics Program-Laboratory Medicine, Sunnybrook Health Sciences CentreDepartment of Medical Biophysics, University of TorontoAbstract Globally, prostate cancer is the second most common malignancy in males, with over 400 thousand men dying from the disease each year. A common treatment modality for localized prostate cancer is radiotherapy. However, up to half of high-risk patients can relapse with radiorecurrent prostate cancer, the aggressive clinical progression of which remains severely understudied. To address this, we have established an orthotopic mouse model for study that recapitulates the aggressive clinical progression of radiorecurrent prostate cancer. Radiorecurrent DU145 cells which survived conventional fraction (CF) irradiation were orthotopically injected into the prostates of athymic nude mice and monitored with bioluminescent imaging. CF tumours exhibited higher take rates and grew more rapidly than treatment-naïve parental tumours (PAR). Pathohistological analysis revealed extensive seminal vesicle invasion and necrosis in CF tumours, recapitulating the aggressive progression towards locally advanced disease exhibited by radiorecurrent tumours clinically. RNA sequencing of CF and PAR tumours identified ROBO1, CAV1, and CDH1 as candidate targets of radiorecurrent progression associated with biochemical relapse clinically. Together, this study presents a clinically relevant orthotopic model of radiorecurrent prostate cancer progression that will enable discovery of targets for therapeutic intervention to improve outcomes in prostate cancer patients.https://doi.org/10.1038/s41598-024-82546-w |
| spellingShingle | Gavin Frame Xiaoyong Huang Roni Haas Kabir A. Khan Hon S. Leong Thomas Kislinger Paul C. Boutros Michelle Downes Stanley K. Liu Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model Scientific Reports |
| title | Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model |
| title_full | Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model |
| title_fullStr | Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model |
| title_full_unstemmed | Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model |
| title_short | Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model |
| title_sort | accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model |
| url | https://doi.org/10.1038/s41598-024-82546-w |
| work_keys_str_mv | AT gavinframe acceleratedgrowthandlocalprogressionofradiorecurrentprostatecancerinanorthotopicbioluminescentmousemodel AT xiaoyonghuang acceleratedgrowthandlocalprogressionofradiorecurrentprostatecancerinanorthotopicbioluminescentmousemodel AT ronihaas acceleratedgrowthandlocalprogressionofradiorecurrentprostatecancerinanorthotopicbioluminescentmousemodel AT kabirakhan acceleratedgrowthandlocalprogressionofradiorecurrentprostatecancerinanorthotopicbioluminescentmousemodel AT honsleong acceleratedgrowthandlocalprogressionofradiorecurrentprostatecancerinanorthotopicbioluminescentmousemodel AT thomaskislinger acceleratedgrowthandlocalprogressionofradiorecurrentprostatecancerinanorthotopicbioluminescentmousemodel AT paulcboutros acceleratedgrowthandlocalprogressionofradiorecurrentprostatecancerinanorthotopicbioluminescentmousemodel AT michelledownes acceleratedgrowthandlocalprogressionofradiorecurrentprostatecancerinanorthotopicbioluminescentmousemodel AT stanleykliu acceleratedgrowthandlocalprogressionofradiorecurrentprostatecancerinanorthotopicbioluminescentmousemodel |