2. Academic Validation
  3. Schwann cells regulate tumor cells and cancer-associated fibroblasts in the pancreatic ductal adenocarcinoma microenvironment

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

  • Nat Commun. 2023 Jul 31;14(1):4600. doi: 10.1038/s41467-023-40314-w.
Meilin Xue # 1 2 3 4,  Youwei Zhu # 1 2 3,  Yongsheng Jiang # 1 2 3,  Lijie Han # 1 2 3,  Minmin Shi 1 2 3,  Rui Su 4,  Liwen Wang 1 2,  Cheng Xiong 1 2 3,  Chaofu Wang 5,  Ting Wang 5,  Shijie Deng 5,  Dong Wu 4,  Yizhi Cao 1 2 3,  Lei Dong 5,  Fan Bai 6,  Shulin Zhao 1 2,  Xiaxing Deng 1 2,  Chenghong Peng 1 2,  Hongwei Li 1 2,  Jianjun Chen 4,  Baiyong Shen 7 8 9,  Lingxi Jiang 10 11,  Hao Chen 12 13 14
Affiliations

Affiliations

  • 1 Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 4 Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA, 91016, USA.
  • 5 Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China.
  • 7 Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shenby@shsmu.edu.cn.
  • 8 Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shenby@shsmu.edu.cn.
  • 9 State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China. shenby@shsmu.edu.cn.
  • 10 Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jlx12120@rjh.com.cn.
  • 11 Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China. jlx12120@rjh.com.cn.
  • 12 Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. haochendr@126.com.
  • 13 Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China. haochendr@126.com.
  • 14 State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China. haochendr@126.com.
  • # Contributed equally.
PMID: 37524695 DOI: 10.1038/s41467-023-40314-w
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.

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