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Orthotopic Mouse Model of Colorectal Cancer
Published on: December 4, 2007
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Cancer-Associated Fibroblasts Establish Spatially Distinct Prognostic Niches in Subcutaneous Colorectal Cancer Mouse
Zhixian Lin1,2, Jinmeng Wang1,2, Yixin Ma2
1Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Cancers
|July 29, 2025
Summary
Spatial transcriptomics revealed two distinct zones in colorectal cancer (CRC) tumors, driven by cancer-associated fibroblasts (CAFs). These zones exhibit unique cellular ecosystems and communication, impacting patient prognosis and therapeutic strategies.
Area of Science:
- Oncology
- Cancer Biology
- Spatial Transcriptomics
Background:
- Subcutaneous tumor models are crucial for colorectal cancer (CRC) research.
- Understanding the spatial organization of the tumor microenvironment (TME) in these models is limited.
Purpose of the Study:
- To systematically characterize spatial heterogeneity within MC38 subcutaneous CRC tumors.
- To elucidate the regulatory mechanisms governing the TME in these models.
Main Methods:
- Application of spatial transcriptomics.
- Analysis of MC38 subcutaneous tumors in a syngeneic mouse model.
Main Results:
- Identification of two spatially distinct tumor zones, separated by cancer-associated fibroblasts (CAFs).
- Zones differ in cellular composition, oncogenic signaling, immune infiltration, and metabolic states.
- Zone-specific communication networks (e.g., ANGPTL4-SDC2, PROS1-AXL) identified, linked to prognosis.
Conclusions:
- Region-specific cellular ecosystems and intercellular crosstalk create prognostically divergent niches in CRC tumors.
- Findings provide insights for developing spatially guided therapeutic strategies.
- Highlights the importance of spatial heterogeneity in CRC tumor biology.
