Schwann cells regulate tumor cells and cancer-associated fibroblasts in the pancreatic ductal adenocarcinoma microenvironment

• Published in: Nature communications Vol. 14; no. 1; p. 4600
• Main Authors: Xue, Meilin, Zhu, Youwei, Jiang, Yongsheng, Han, Lijie, Shi, Minmin, Su, Rui, Wang, Liwen, Xiong, Cheng, Wang, Chaofu, Wang, Ting, Deng, Shijie, Wu, Dong, Cao, Yizhi, Dong, Lei, Bai, Fan, Zhao, Shulin, Deng, Xiaxing, Peng, Chenghong, Li, Hongwei, Chen, Jianjun, Shen, Baiyong, Jiang, Lingxi, Chen, Hao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31-07-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/105; 13/106; 13/21; 13/51; 38/77; 49/39; 49/91; 631/67/327; 692/4020/1503/1504/1713; 82/58; Adenocarcinoma; Cancer; Cancer-Associated Fibroblasts - metabolism; Carcinoma, Pancreatic Ductal - pathology; Cell culture; Cell Line, Tumor; Cell migration; Cell proliferation; DNA microarrays; Fibroblasts; Fibroblasts - metabolism; Gene sequencing; Humanities and Social Sciences; Humans; Inflammation; Interleukins; Microenvironments; Midkine; multidisciplinary; Pancreas; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - pathology; Peripheral nerves; Peripheral neuropathy; Schwann cells; Schwann Cells - metabolism; Science; Science (multidisciplinary); Spatial analysis; Stroma; Transcriptomes; Tumor cells; Tumor Microenvironment - genetics; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-40314-w

Neuropathy is a feature more frequently observed in pancreatic ductal adenocarcinoma (PDAC) than other tumors. Schwann cells, the most prevalent cell type 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, here we perform single-cell RNA-sequencing and microarray-based spatial transcriptome analysis of PDAC tissues. Results suggest 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 demonstrate that Schwann cells enhance the proliferation and migration of PDAC cells via Midkine signaling and promote the switch of CAFs to iCAFs via interleukin-1α. Culture of tumor cells and CAFs with Schwann cells conditioned medium accelerates PDAC progression. Thus, we reveal that Schwann cells induce malignant subtypes of tumor cells and CAFs in the PDAC milieu.
The effects of Schwann cells on the neuro-stroma niche in pancreatic ductal adenocarcinoma (PDAC) remain to be explored. Here, single-cell RNA-sequencing and spatial transcriptome analysis of PDAC tissues reveal that Schwann cells induce malignant subtypes of tumour cells and cancer associated fibroblasts.