Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics
BackgroundProstate cancer (PCa) presents substantial heterogeneity and unpredictability in its progression. Despite therapeutic advancements, mortality from advanced PCa remains a significant challenge. Understanding the intercellular communication within the tumor microenvironment (TME) is critical...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1560998/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850135803482603520 |
|---|---|
| author | Tingting Wu Xinyu Li Fei Zheng Hanchao Liu Yang Yu |
| author_facet | Tingting Wu Xinyu Li Fei Zheng Hanchao Liu Yang Yu |
| author_sort | Tingting Wu |
| collection | DOAJ |
| description | BackgroundProstate cancer (PCa) presents substantial heterogeneity and unpredictability in its progression. Despite therapeutic advancements, mortality from advanced PCa remains a significant challenge. Understanding the intercellular communication within the tumor microenvironment (TME) is critical for uncovering mechanisms driving tumorigenesis and identifying novel therapeutic targets.MethodsWe employed an integrative approach combining bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics to investigate interactions between FAP+ fibroblasts and tumor-associated macrophages in PCa. Key findings were validated using immunohistochemical and immunofluorescence staining techniques.ResultsAnalysis of 23,519 scRNA-seq data from 23 prostate samples revealed a pronounced accumulation of FAP+ fibroblasts in tumor tissues. Spatial transcriptomics and bulk RNA sequencing demonstrated strong associations between FAP+ fibroblasts and SPP1+ macrophages. Notably, tumor-specific intercellular signaling pathways, such as CSF1/CSF1R and CXCL/ACKR1, were identified, highlighting their potential role in fostering an immunosuppressive TME.ConclusionOur findings unveil a distinct pattern of crosstalk between FAP+ fibroblasts and SPP1+ macrophages in PCa, shedding light on potential therapeutic targets for advanced PCa. |
| format | Article |
| id | doaj-art-b52fea93636a43a1ac98ef8df3f79437 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b52fea93636a43a1ac98ef8df3f794372025-08-20T02:31:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15609981560998Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omicsTingting Wu0Xinyu Li1Fei Zheng2Hanchao Liu3Yang Yu4Department of General Surgery, Shenzhen Qianhai Taikang Hospital, Shenzhen, ChinaDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Andrology and Urology, Sir Run Shaw Hospital, affiliated with the Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaDepartment of General Surgery, Chifeng Hospital, Chifeng, Inner Mongolia, ChinaBackgroundProstate cancer (PCa) presents substantial heterogeneity and unpredictability in its progression. Despite therapeutic advancements, mortality from advanced PCa remains a significant challenge. Understanding the intercellular communication within the tumor microenvironment (TME) is critical for uncovering mechanisms driving tumorigenesis and identifying novel therapeutic targets.MethodsWe employed an integrative approach combining bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics to investigate interactions between FAP+ fibroblasts and tumor-associated macrophages in PCa. Key findings were validated using immunohistochemical and immunofluorescence staining techniques.ResultsAnalysis of 23,519 scRNA-seq data from 23 prostate samples revealed a pronounced accumulation of FAP+ fibroblasts in tumor tissues. Spatial transcriptomics and bulk RNA sequencing demonstrated strong associations between FAP+ fibroblasts and SPP1+ macrophages. Notably, tumor-specific intercellular signaling pathways, such as CSF1/CSF1R and CXCL/ACKR1, were identified, highlighting their potential role in fostering an immunosuppressive TME.ConclusionOur findings unveil a distinct pattern of crosstalk between FAP+ fibroblasts and SPP1+ macrophages in PCa, shedding light on potential therapeutic targets for advanced PCa.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1560998/fullprostate cancertumor microenvironmentcellular crosstalksingle-cell RNA sequencingspatial transcriptomicsFAP+ fibroblasts |
| spellingShingle | Tingting Wu Xinyu Li Fei Zheng Hanchao Liu Yang Yu Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics Frontiers in Immunology prostate cancer tumor microenvironment cellular crosstalk single-cell RNA sequencing spatial transcriptomics FAP+ fibroblasts |
| title | Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics |
| title_full | Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics |
| title_fullStr | Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics |
| title_full_unstemmed | Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics |
| title_short | Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics |
| title_sort | intercellular communication between fap fibroblasts and spp1 macrophages in prostate cancer via multi omics |
| topic | prostate cancer tumor microenvironment cellular crosstalk single-cell RNA sequencing spatial transcriptomics FAP+ fibroblasts |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1560998/full |
| work_keys_str_mv | AT tingtingwu intercellularcommunicationbetweenfapfibroblastsandspp1macrophagesinprostatecancerviamultiomics AT xinyuli intercellularcommunicationbetweenfapfibroblastsandspp1macrophagesinprostatecancerviamultiomics AT feizheng intercellularcommunicationbetweenfapfibroblastsandspp1macrophagesinprostatecancerviamultiomics AT hanchaoliu intercellularcommunicationbetweenfapfibroblastsandspp1macrophagesinprostatecancerviamultiomics AT yangyu intercellularcommunicationbetweenfapfibroblastsandspp1macrophagesinprostatecancerviamultiomics |