articleCancer ResearchMar 26, 2025HYBRID OA

Cancer-Associated Fibroblasts Foster a High-Lactate Microenvironment to Drive Perineural Invasion in Pancreatic Cancer

Guangdong General Hospital · Guangdong Academy of Medical Sciences · +5 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Perineural invasion (PNI) is a pivotal prognostic factor in pancreatic cancer, associated with aggressive tumor behavior and adverse patient outcomes. The recognized clinical impact of PNI highlights the need to better understand the molecular mechanisms underlying PNI-induced phenotypes. In this study, we isolated PNI-associated cancer-associated fibroblasts (pCAF), which demonstrated a markedly enhanced capacity to promote neural invasion in pancreatic cancer compared with non-PNI-associated CAFs. Single-cell, high-throughput sequencing and metabolomics data showed a significant upregulation of glycolysis in pCAFs, fostering a high-lactate tumor microenvironment conducive to cancer progression. pCAF-derived…

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