Andrology-Open Access
Open Access

Abstract

Crosstalk between FAP+ Fibroblasts and Tumor-Associated Macrophages in Prostate Cancer Unveiled by Single-Cell Sequencing and Spatial Transcriptomics

Xinyu Li*, Fei Zheng, Zepeng Dong, Hanchao Liu and Tingting Wu*

Background: Prostate Cancer (PCa) has a wide range of diversity and uncertainty in tumor progression. Despite the availability of multidisciplinary therapy, the mortality of patients with advanced PCa still remains high. In-depth research of the intercellular communications in the Tumor Microenvironment (TME) will improve our understanding of the tumorigenesis mechanism of PCa and bring up potential therapeutic targets to patients with PCa.

Methods: We integrate data including bulk RNA sequencing, single-cell RNA sequencing and spatial transcriptomics to investigate the intercellular communications between FAP+fibroblasts and tumor-associated macrophages in PCa. Immumohistochemical and immunofluorescence staining were performed for verification of the analysis.

Results: We analyzed single-cell sequencing data encompassing 23,519 cells across 23 prostate samples, including normal and tumor tissues. A remarkable increase in the number of FAP+fibroblasts within tumor tissues was observed. By analyzing spatial transcriptomics and bulk RNA sequencing data, we observed a notable correlation between FAP+fibroblasts and tumor- associated macrophages (particularly SPP1+macrophages). Compared to normal tissues, tumor tissues exhibited specific intercellular communication between FAP+fibroblasts and SPP1+ macrophages, including CSF1/CSF1R, CXCL/ACKR1 and other tumor-promoting signaling pathways, which could potentially reshape the TME in an unfavorable manner.

Conclusion: Our research identified a unique pattern of interactions between FAP+fibroblasts and SPP1 +macrophages in PCa, providing potential therapeutic targets for the treatment of patients with PCa.

Published Date: 2025-10-20; Received Date: 2024-09-19