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Integrated Single-Cell and Spatial Profiling of MMP Gene Expression in Colorectal Cancer.

Nicholas A Danese1, Shan Kurkcu1, Marina Bleiler1

  • 1Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269-3125.

Biorxiv : the Preprint Server for Biology
|May 4, 2026
PubMed
Summary
This summary is machine-generated.

Matrix metalloproteinases (MMPs) play varied roles in colorectal cancer (CRC) progression. Different cell types, including cancer-associated fibroblasts and myeloid cells, express specific MMPs, influencing tumor spread and malignancy risk.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Matrix metalloproteinases (MMPs) are known to be upregulated in colorectal cancers (CRCs).
  • The specific roles and interactions of different MMPs in CRC progression remain incompletely understood.

Purpose of the Study:

  • To investigate the cell-type-specific and spatial expression patterns of MMPs in CRCs.
  • To understand how MMP expression by various cell types contributes to colorectal cancer progression and metastasis.

Main Methods:

  • Analysis of single-cell and spatial transcriptomic data from colorectal cancer samples.
  • Characterization of MMP expression profiles in distinct cell populations, including cancer-associated fibroblasts (CAFs), myeloid cells, and cancer cells.
  • In vitro validation of MMP expression stability in CAFs.

Main Results:

  • Identified distinct CAF subtypes expressing different MMP combinations (e.g., MMP1/3, MMP11).
  • Myeloid cells expressed specific MMPs (9, 12, 14) correlating with secretory gene expression.
  • A subset of cancer cells expressed high MMP7, often co-expressing MMP1, MMP14, and Wnt-related genes, indicating high metastatic potential.
  • Spatial analysis revealed MMP expression clusters linked to cell-type localization and proximity.
  • MMP1 expression in CAFs was a stable phenotype, often found at the stromal interface, suggesting a role in cell migration.

Conclusions:

  • Cell-type and spatial MMP expression patterns are heterogeneous across colorectal tumors.
  • These variations in MMP expression likely contribute to differences in tumor progression and metastasis.
  • Specific MMPs expressed by different cell types may represent potential therapeutic targets for managing CRC spread.