Irradiation of prostate cancer alters circulating small extracellular vesicle functions
Abstract It is known that β1 integrins and a downstream signaling molecule c-Src are upregulated in prostate cancer (PrCa) tissues, are co-expressed in circulating small extracellular vesicles (sEVs) and contribute to cancer progression. Here, we demonstrate that sEVs from PrCa patients show robust...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-03329-5 |
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| author | Aejaz Sayeed Vaughn Garcia Cecilia E. Verrillo Rachel M. DeRita Md Niamat Hossain Shiv Ram Krishn Samuel Sey Christopher D. Shields Adrian D. Altieri Qin Liu Khalid Sossey-Alaoui William K. Kelly Lucia R. Languino |
| author_facet | Aejaz Sayeed Vaughn Garcia Cecilia E. Verrillo Rachel M. DeRita Md Niamat Hossain Shiv Ram Krishn Samuel Sey Christopher D. Shields Adrian D. Altieri Qin Liu Khalid Sossey-Alaoui William K. Kelly Lucia R. Languino |
| author_sort | Aejaz Sayeed |
| collection | DOAJ |
| description | Abstract It is known that β1 integrins and a downstream signaling molecule c-Src are upregulated in prostate cancer (PrCa) tissues, are co-expressed in circulating small extracellular vesicles (sEVs) and contribute to cancer progression. Here, we demonstrate that sEVs from PrCa patients show robust expression of both β1 integrins and c-Src. The impact of irradiation, a widely used therapy for the treatment of PrCa, on circulating sEVs is however not fully understood. We show that sEVs isolated from the plasma of transgenic adenocarcinoma of mouse prostate (TRAMP) mice, stimulate migration and anchorage-independent growth of recipient cancer cells, but sEVs are not active when isolated from mice that had undergone pelvic irradiation of PrCa. In addition, circulating sEVs from irradiated mice do not show co-sedimentation of β1 integrins and either c-Src or sEV markers, previously observed in sEVs from non-irradiated mice, but show reduced expression of c-Src. To rule out that the observed effect of irradiation on sEVs is not due to reduced tumor size, we demonstrate that irradiation of PrCa cells in vitro diminishes sEV capability to stimulate recipient cell anchorage-independent growth. Irradiation-induced changes in the composition of circulating sEVs illustrate a tumor-suppressive effect of radiation, which may have potential therapeutic implications. |
| format | Article |
| id | doaj-art-af53cd1b289849cbabc731a812b0d8ce |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-af53cd1b289849cbabc731a812b0d8ce2025-08-20T03:45:28ZengNature PortfolioScientific Reports2045-23222025-07-0115111010.1038/s41598-025-03329-5Irradiation of prostate cancer alters circulating small extracellular vesicle functionsAejaz Sayeed0Vaughn Garcia1Cecilia E. Verrillo2Rachel M. DeRita3Md Niamat Hossain4Shiv Ram Krishn5Samuel Sey6Christopher D. Shields7Adrian D. Altieri8Qin Liu9Khalid Sossey-Alaoui10William K. Kelly11Lucia R. Languino12Prostate Cancer Discovery and Development Program, Thomas Jefferson UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityMolecular and Cellular Oncogenesis Program, The Wistar InstituteDepartment of Medicine, School of Medicine MetroHealth Medical Center Rammelkamp Center for Research, Case Western Reserve UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityProstate Cancer Discovery and Development Program, Thomas Jefferson UniversityAbstract It is known that β1 integrins and a downstream signaling molecule c-Src are upregulated in prostate cancer (PrCa) tissues, are co-expressed in circulating small extracellular vesicles (sEVs) and contribute to cancer progression. Here, we demonstrate that sEVs from PrCa patients show robust expression of both β1 integrins and c-Src. The impact of irradiation, a widely used therapy for the treatment of PrCa, on circulating sEVs is however not fully understood. We show that sEVs isolated from the plasma of transgenic adenocarcinoma of mouse prostate (TRAMP) mice, stimulate migration and anchorage-independent growth of recipient cancer cells, but sEVs are not active when isolated from mice that had undergone pelvic irradiation of PrCa. In addition, circulating sEVs from irradiated mice do not show co-sedimentation of β1 integrins and either c-Src or sEV markers, previously observed in sEVs from non-irradiated mice, but show reduced expression of c-Src. To rule out that the observed effect of irradiation on sEVs is not due to reduced tumor size, we demonstrate that irradiation of PrCa cells in vitro diminishes sEV capability to stimulate recipient cell anchorage-independent growth. Irradiation-induced changes in the composition of circulating sEVs illustrate a tumor-suppressive effect of radiation, which may have potential therapeutic implications.https://doi.org/10.1038/s41598-025-03329-5β1 integrin subunitc-SrcSmall extracellular vesiclesProstate cancerTRAMPIrradiation |
| spellingShingle | Aejaz Sayeed Vaughn Garcia Cecilia E. Verrillo Rachel M. DeRita Md Niamat Hossain Shiv Ram Krishn Samuel Sey Christopher D. Shields Adrian D. Altieri Qin Liu Khalid Sossey-Alaoui William K. Kelly Lucia R. Languino Irradiation of prostate cancer alters circulating small extracellular vesicle functions Scientific Reports β1 integrin subunit c-Src Small extracellular vesicles Prostate cancer TRAMP Irradiation |
| title | Irradiation of prostate cancer alters circulating small extracellular vesicle functions |
| title_full | Irradiation of prostate cancer alters circulating small extracellular vesicle functions |
| title_fullStr | Irradiation of prostate cancer alters circulating small extracellular vesicle functions |
| title_full_unstemmed | Irradiation of prostate cancer alters circulating small extracellular vesicle functions |
| title_short | Irradiation of prostate cancer alters circulating small extracellular vesicle functions |
| title_sort | irradiation of prostate cancer alters circulating small extracellular vesicle functions |
| topic | β1 integrin subunit c-Src Small extracellular vesicles Prostate cancer TRAMP Irradiation |
| url | https://doi.org/10.1038/s41598-025-03329-5 |
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