Schwann Cells Shape Tumor Cells and Cancer-Associated Fibroblasts in the Pancreatic Ductal Adenocarcinoma Microenvironment

Neuropathy is a feature more frequently observed in pancreatic ductal adenocarcinoma (PDAC) than other tumors. Schwann cells, the most prevalent cell in peripheral nerves, migrate toward tumor cells and associate with poor prognosis in PDAC. To unveil the effects of Schwann cells on the neuro-stroma niche, single-cell RNA-sequencing and microarray-based spatial transcriptome analysis of PDAC tissues were performed. Results suggested that Schwann cells may drive tumor cells and cancer-associated fibroblasts (CAFs) to more malignant subtypes: basal-like and inflammatory CAFs (iCAFs), respectively. Moreover, in vitro and in vivo assays demonstrated that Schwann cells enhanced the proliferation and migration of PDAC cells via Midkine and promoted the switch of CAFs to iCAFs via interleukin-1a. By Schwann cells condition medium, tumor cells together with iCAFs accelerate PDAC progression. Thus, we revealed, for the first time, that Schwann cells induce malignant subtypes of tumor cells and CAFs in the PDAC milieu. Overall design: Bulk-RNA sequence was performed in tumor cells and CAFs with or without Schwann cells condition medium (CM) treatment