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

Meilin Xue, Youwei Zhu, Yongsheng Jiang, Lijie Han, Minmin Shi, Rui Su, Liwen Wang, Cheng Xiong, Chaofu Wang, Ting Wang, Shijie Deng, Dong Wu, Yizhi Cao, Lei Dong, Fan Bai, Shulin Zhao, Xiaxing Deng, Chenghong Peng, Hongwei Li, Jianjun Chen, Baiyong Shen (), Lingxi Jiang () and Hao Chen ()
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Meilin Xue: Shanghai Jiao Tong University School of Medicine
Youwei Zhu: Shanghai Jiao Tong University School of Medicine
Yongsheng Jiang: Shanghai Jiao Tong University School of Medicine
Lijie Han: Shanghai Jiao Tong University School of Medicine
Minmin Shi: Shanghai Jiao Tong University School of Medicine
Rui Su: Beckman Research Institute of City of Hope
Liwen Wang: Shanghai Jiao Tong University School of Medicine
Cheng Xiong: Shanghai Jiao Tong University School of Medicine
Chaofu Wang: Shanghai Jiao Tong University School of Medicine
Ting Wang: Shanghai Jiao Tong University School of Medicine
Shijie Deng: Shanghai Jiao Tong University School of Medicine
Dong Wu: Beckman Research Institute of City of Hope
Yizhi Cao: Shanghai Jiao Tong University School of Medicine
Lei Dong: Shanghai Jiao Tong University School of Medicine
Fan Bai: Peking University
Shulin Zhao: Shanghai Jiao Tong University School of Medicine
Xiaxing Deng: Shanghai Jiao Tong University School of Medicine
Chenghong Peng: Shanghai Jiao Tong University School of Medicine
Hongwei Li: Shanghai Jiao Tong University School of Medicine
Jianjun Chen: Beckman Research Institute of City of Hope
Baiyong Shen: Shanghai Jiao Tong University School of Medicine
Lingxi Jiang: Shanghai Jiao Tong University School of Medicine
Hao Chen: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-40314-w

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