SPP1 is required for maintaining mesenchymal cell fate in pancreatic cancer.

ABSTRACT: Elucidating the complex network of communication between tumour cells is central to understanding cell fate decisions and progression of pancreatic ductal adenocarcinoma (PDAC)^1,2. We previously showed that constant suppression of BMP activity by the BMP antagonist GREM1 secreted by mesenchymal PDAC cells is essential for maintaining the fate of epithelial PDAC cells³. Here we identify SPP1 (also known as osteopontin)⁴ as a key regulator of mesenchymal cell fate in pancreatic cancer. Proteomic analysis of plasma from patients with PDAC showed that SPP1 is substantially upregulated in late-stage disease. Inactivation of Spp1 led to a delay in tumorigenesis in mouse PDAC models and abolished metastasis formation. Spp1 was expressed in epithelial PDAC cells, a

SUBMITTER: Li H 

PROVIDER: S-EPMC12675285 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature