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Single-nucleus RNA sequencing and spatial transcriptomics reveal an immunosuppressive tumor microenvironment related to metastatic dissemination during pancreatic cancer liver metastasis

  • 0Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China.
Theranostics +

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April 30, 2025

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April 30, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Pancreatic cancer liver metastasis involves immune cell changes and epithelial-mesenchymal transition. The study identifies CITED4 as a key factor promoting cancer spread and poor outcomes.

Area Of Science

  • Oncology
  • Immunology
  • Genomics

Background

  • Pancreatic ductal adenocarcinoma (PDAC) is aggressive with high mortality and early liver metastasis.
  • The tumor microenvironment's role in PDAC progression is significant, but its immune component in liver metastasis is unclear.

Purpose Of The Study

  • Investigate cellular and immune heterogeneity in primary and metastatic PDAC tissues.
  • Elucidate mechanisms driving PDAC liver metastasis and identify prognostic biomarkers.
  • Analyze the role of CITED4 in pancreatic cancer invasion and metastasis.

Main Methods

  • Single-nucleus RNA sequencing and spatial transcriptomics on primary tumor and liver metastasis tissues.
  • Deconvolution, intercellular signaling analysis, and immune infiltration profiling.
  • Multiplexed immunofluorescence staining, immunohistochemistry, transwell assays, and scratch wound healing assays.

Main Results

  • Metastatic cells showed increased epithelial-mesenchymal transition (EMT) gene expression.
  • Primary tumors had enriched metastatic cells and regulatory T (Treg) cells at the tumor front, creating an immunosuppressive microenvironment.
  • The SPP1 pathway was identified as a key mediator of immunosuppression; CITED4 was a prognostic biomarker linked to liver metastasis and poor survival.

Conclusions

  • Regulatory T cell alterations, driven by metastatic cells, significantly contribute to PDAC liver metastasis.
  • CITED4 enhances the metastatic potential of pancreatic cancer cells and is a potential therapeutic target.

Keywords: