Intercellular communication between FAP+ fibroblasts and SPP1+ macrophages in prostate cancer via multi-omics.

BACKGROUND: Prostate 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.

METHODS: We 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.

RESULTS: Analysis 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.

CONCLUSION: Our findings unveil a distinct pattern of crosstalk between FAP+ fibroblasts and SPP1+ macrophages in PCa, shedding light on potential therapeutic targets for advanced PCa.