POSTN+ cancer-associated fibroblasts promote bladder cancer progression via angiogenesis and immune modulation: an...

Bladder cancer (BCa) progression is driven by the tumor microenvironment, with cancer-associated fibroblasts (CAFs) playing a pivotal role. Periostin (POSTN), secreted by CAFs, is linked to tumor malignancy, but its specific role in BCa remains unclear.

This study is a secondary analysis of publicly available single-cell and bulk transcriptomic data. Single-cell RNA sequencing (scRNA-seq) data from four BCa and four control samples were analyzed to construct a transcriptomic atlas. CAFs and monocytes were subclustered, and POSTN+ CAFs were characterized using differential gene expression, GSVA, and KEGG analyses. CellChat and NicheNet assessed cell-cell communication. TCGA data were used to validate POSTN's prognostic significance. Additionally, POSTN expression was detected in transfected CAF cell lines, and scratch and invasion assays were performed using the co-culture system of CAFs and bladder cancer cells (T24).

Nine cell clusters were identified, with monocytes and CAFs enriched in BCa. POSTN+ CAFs, significantly increased in BCa, promoted angiogenesis, migration, and invasion. CellChat revealed enhanced CAF-monocyte communication via the IL1B/IL1R1 axis, contributing to an immunosuppressive microenvironment. KLRC1+ monocytes were enriched in BCa, regulating cell cycle and angiogenesis. Pseudotime analysis showed CAFs' differentiation toward pro-tumorigenic states. TCGA analysis confirmed POSTN's upregulation and association with poor prognosis (P < 0.05). Functional assays revealed CAFs markedly enhanced T24 migration and invasion, and POSTN knockdown suppressed this CAF-induced effect (P < 0.01).

POSTN+ CAFs drive BCa progression by enhancing angiogenesis, migration, and immune suppression, mediated partly by the IL1B/IL1R1 axis.