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Updated: May 23, 2025
10:43
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
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Single-cell multi-stage spatial evolutional map of esophageal carcinogenesis
Jiang Chang1, Junting Lu2, Qingyi Liu2
1Department of Health Toxicology, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cancer Cell
|March 11, 2025
Summary
Cancer progression involves cell and microenvironment co-evolution. A spatial map revealed a specific cell type disrupting tissue barriers and recruiting fibroblasts, forming a niche that shields tumors and impacts patient outcomes in esophageal squamous cell carcinoma.
Area of Science:
- Oncology
- Cell Biology
- Cancer Research
Background:
- Cancer development is a complex interplay between malignant cells and their microenvironment.
- Understanding the spatial dynamics of this interaction is crucial for deciphering cancer progression.
- The physical architecture and cellular communication within the tumor microenvironment remain poorly understood.
Purpose of the Study:
- To create a high-resolution spatial transcriptomic map of human esophageal squamous cell carcinoma (ESCC).
- To chart the evolutionary trajectories of cancer cells within their microenvironment.
- To identify key cellular interactions driving ESCC progression and their clinical implications.
Main Methods:
- Spatial transcriptomics at single-cell resolution.
- Analysis of 127 multi-stage fields of view from 43 ESCC patients.
- Mapping the evolutionary paths of over 6.4 million cells.
Main Results:
- Identified a proliferative epithelial cell subpopulation driving ESCC progression.
- Demonstrated that these cells acquire dedifferentiated and invasive traits.
- Revealed recruitment of normal fibroblasts into cancer-associated fibroblasts (CAFs) via JAG1-NOTCH1 signaling at the precancerous stage.
- Discovered the formation of a protective "CAF-Epi" niche at the tumor edge, shielding from immune surveillance.
Conclusions:
- CAF-Epi niche formation is a critical indicator of ESCC progression and impacts patient outcomes.
- This mechanism is relevant not only in ESCC but also in other squamous cell carcinomas.
- Spatial mapping provides critical insights into cancer evolution and microenvironment interactions.
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