Identification of functional and diverse circulating cancer‐associated fibroblasts in metastatic castration‐naïve prostate cancer patients
In prostate cancer (PCa), cancer‐associated fibroblasts (CAFs) promote tumor progression, drug resistance, and metastasis. Although circulating tumor cells are studied as prognostic and diagnostic markers, little is known about other circulating cells and their association with PCa metastasis. Here,...
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| Format: | Article |
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Wiley
2025-07-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13653 |
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| author | Richell Booijink Leon W. M. M. Terstappen Eshwari Dathathri Khrystany Isebia Jaco Kraan John Martens Ruchi Bansal |
| author_facet | Richell Booijink Leon W. M. M. Terstappen Eshwari Dathathri Khrystany Isebia Jaco Kraan John Martens Ruchi Bansal |
| author_sort | Richell Booijink |
| collection | DOAJ |
| description | In prostate cancer (PCa), cancer‐associated fibroblasts (CAFs) promote tumor progression, drug resistance, and metastasis. Although circulating tumor cells are studied as prognostic and diagnostic markers, little is known about other circulating cells and their association with PCa metastasis. Here, we explored the presence of circulating CAFs (cCAFs) in metastatic castration‐naïve prostate cancer (mCNPC) patients. cCAFs were stained with fibroblast activation protein (FAP), epithelial cell adhesion molecule (EpCAM), and receptor‐type tyrosine‐protein phosphatase C (CD45), then FAP+EpCAM− cCAFs were enumerated and sorted using fluorescence‐activated cell sorting. FAP+EpCAM− cCAFs ranged from 60 to 776 (389 mean ± 229 SD) per 2 × 108 mononuclear cells, whereas, in healthy donors, FAP+ EpCAM− cCAFs ranged from 0 to 71 (28 mean ± 22 SD). The mCNPC‐derived cCAFs showed positivity for vimentin and intracellular collagen‐I. They were viable and functional after sorting, as confirmed by single‐cell collagen‐I secretion after 48 h of culturing. Two cCAF subpopulations, FAP+CD45− and FAP+CD45+, were identified, both expressing collagen‐I and vimentin, but with distinctly different morphologies. Collectively, this study demonstrates the presence of functional and viable circulating CAFs in mCNPC patients, suggesting the role of these cells in prostate cancer. |
| format | Article |
| id | doaj-art-00b22fbdea0f46edb758521fb0c6c88b |
| institution | Matheson Library |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-00b22fbdea0f46edb758521fb0c6c88b2025-07-08T04:38:21ZengWileyMolecular Oncology1574-78911878-02612025-07-011972074209110.1002/1878-0261.13653Identification of functional and diverse circulating cancer‐associated fibroblasts in metastatic castration‐naïve prostate cancer patientsRichell Booijink0Leon W. M. M. Terstappen1Eshwari Dathathri2Khrystany Isebia3Jaco Kraan4John Martens5Ruchi Bansal6Personalized Diagnostics and Therapeutics, Department of Bioengineering Technologies, Technical Medical Centre, Faculty of Science and Technology University of Twente Enschede The NetherlandsDepartment of Medical Cell BioPhysics, Technical Medical Centre, Faculty of Science and Technology University of Twente Enschede The NetherlandsDepartment of Medical Cell BioPhysics, Technical Medical Centre, Faculty of Science and Technology University of Twente Enschede The NetherlandsDepartment of Medical Oncology Erasmus MC Cancer Institute, University Medical Center Rotterdam The NetherlandsDepartment of Medical Oncology Erasmus MC Cancer Institute, University Medical Center Rotterdam The NetherlandsDepartment of Medical Oncology Erasmus MC Cancer Institute, University Medical Center Rotterdam The NetherlandsPersonalized Diagnostics and Therapeutics, Department of Bioengineering Technologies, Technical Medical Centre, Faculty of Science and Technology University of Twente Enschede The NetherlandsIn prostate cancer (PCa), cancer‐associated fibroblasts (CAFs) promote tumor progression, drug resistance, and metastasis. Although circulating tumor cells are studied as prognostic and diagnostic markers, little is known about other circulating cells and their association with PCa metastasis. Here, we explored the presence of circulating CAFs (cCAFs) in metastatic castration‐naïve prostate cancer (mCNPC) patients. cCAFs were stained with fibroblast activation protein (FAP), epithelial cell adhesion molecule (EpCAM), and receptor‐type tyrosine‐protein phosphatase C (CD45), then FAP+EpCAM− cCAFs were enumerated and sorted using fluorescence‐activated cell sorting. FAP+EpCAM− cCAFs ranged from 60 to 776 (389 mean ± 229 SD) per 2 × 108 mononuclear cells, whereas, in healthy donors, FAP+ EpCAM− cCAFs ranged from 0 to 71 (28 mean ± 22 SD). The mCNPC‐derived cCAFs showed positivity for vimentin and intracellular collagen‐I. They were viable and functional after sorting, as confirmed by single‐cell collagen‐I secretion after 48 h of culturing. Two cCAF subpopulations, FAP+CD45− and FAP+CD45+, were identified, both expressing collagen‐I and vimentin, but with distinctly different morphologies. Collectively, this study demonstrates the presence of functional and viable circulating CAFs in mCNPC patients, suggesting the role of these cells in prostate cancer.https://doi.org/10.1002/1878-0261.13653circulating cancer‐associated fibroblastcirculating tumor cellsfibroblast‐activated proteinliquid biopsymetastatic prostate cancer |
| spellingShingle | Richell Booijink Leon W. M. M. Terstappen Eshwari Dathathri Khrystany Isebia Jaco Kraan John Martens Ruchi Bansal Identification of functional and diverse circulating cancer‐associated fibroblasts in metastatic castration‐naïve prostate cancer patients Molecular Oncology circulating cancer‐associated fibroblast circulating tumor cells fibroblast‐activated protein liquid biopsy metastatic prostate cancer |
| title | Identification of functional and diverse circulating cancer‐associated fibroblasts in metastatic castration‐naïve prostate cancer patients |
| title_full | Identification of functional and diverse circulating cancer‐associated fibroblasts in metastatic castration‐naïve prostate cancer patients |
| title_fullStr | Identification of functional and diverse circulating cancer‐associated fibroblasts in metastatic castration‐naïve prostate cancer patients |
| title_full_unstemmed | Identification of functional and diverse circulating cancer‐associated fibroblasts in metastatic castration‐naïve prostate cancer patients |
| title_short | Identification of functional and diverse circulating cancer‐associated fibroblasts in metastatic castration‐naïve prostate cancer patients |
| title_sort | identification of functional and diverse circulating cancer associated fibroblasts in metastatic castration naive prostate cancer patients |
| topic | circulating cancer‐associated fibroblast circulating tumor cells fibroblast‐activated protein liquid biopsy metastatic prostate cancer |
| url | https://doi.org/10.1002/1878-0261.13653 |
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