Work

Rewiring the neural niche: Prostaglandin E2 promotes Schwann cell–mediated perineural invasion in pancreatic cancer

Year: 2026

Type: article

Abstract: Pancreatic ductal adenocarcinoma Perineural invasion Prostaglandin E 2 Schwann cell dedifferentiation Tumor-neural nichePancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies.In addition to its dense desmoplastic stroma and propensity for early metastatic spread, PDAC is characterized by extensive interactions with peripheral nerves. 1 Perineural invasion (PNI), defined as tumor cell invasion within, around, or through nerves, is frequently detected in resected PDAC specimens and is associated with local recurrence, pain, metastasis, and poor survival.2 Despite its clinical significance, PNI has historically been regarded primarily as a histopathological feature of PDAC rather than as a dynamic biological process that could potentially be therapeutically targeted.3 An important unresolved question is how pancreatic cancer cells and neural components interact across the tumor microenvironment to establish and promote directional PNI.In a recent study published in Signal Transduction and Targeted Therapy, Wang et al. identified a tumor-derived prostaglandin E 2 (PGE 2 )-Schwann cell axis that promotes PNI in PDAC. 4 Their findings support a model in which PNI is not simply passive tumor extension along pre-existing neural structures but involves active remodeling of the neural microenvironment, whereby pancreatic cancer cell-derived PGE 2 induces a repair-like, pro-invasive phenotype in Schwann cells.This mechanistic insight advances the understanding of PNI by highlighting coordinated interactions among tumor cells, Schwann cells, the extracellular matrix, and axons that facilitate neural invasion.Schwann cells are the major glial cells of the peripheral nervous system.Following peripheral nerve injury, differentiated Schwann cells undergo extensive transcriptional and phenotypic reprogramming to acquire a specialized "repair" phenotype characterized by enhanced migration and elongation, secretion of neurotrophic factors, and formation of cellular structures that support axonal regeneration.5 In PDAC, components of this injury-response program may be co-opted to facilitate tumor progression.Schwann cells are recruited to early neoplastic lesions, promote cancer cell dispersion, and contribute to tumor-nerve crosstalk.6 However, the tumor-derived signals that induce and regulate this Schwann cell phenotype in PDAC have remained incompletely understood.The study by Wang et al. integrates clinical pathological assessment with spatial transcriptomics, single-cell analysis, and functional models to characterize PNI across multiple biological scales.Rather than

Source: iLiver

DOI: 10.1016/j.iliver.2026.100268

Authors: Pengfei Wang, Guangsheng Yang, Tanqing Long, Qi Wang, Juan Liu, Xuedong Wang

Institutions: Beijing Tsinghua Chang Gung Hospital, Tsinghua University, Central Hospital of Zibo, Beijing University of Chinese Medicine

Language: English

Topic: Pancreatic and Hepatic Oncology Research

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,600