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Evaluation of Metaplastic Triple-Negative Breast Cancer Extracellular Matrix Structure and Protein Composition.

Jonathan J Savoie1, Katherine L Hebert2, Connor T King1

  • 1Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA 70803, USA.

Bioengineering (Basel, Switzerland)
|January 28, 2026
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Summary

This study reveals unique extracellular matrix changes in metaplastic triple-negative breast cancer (TNBC), highlighting altered stiffness and protein composition that may drive tumor progression.

Keywords:
MFAP2extracellular matrixmetaplastic breast cancer

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Area of Science:

  • Oncology
  • Biochemistry
  • Materials Science

Background:

  • Tumor progression is linked to extracellular matrix (ECM) alterations and increased matrix stiffness.
  • Previous studies noted ECM protein enrichment in breast tumors, but rare types like metaplastic breast cancer lack comprehensive analysis.
  • Understanding the ECM's role in rare breast cancers is crucial for targeted therapies.

Purpose of the Study:

  • To investigate ECM composition and structural architecture in metaplastic triple-negative breast cancer (TNBC).
  • To identify specific ECM protein alterations and their impact on tumor behavior.
  • To establish an extracellular signature for metaplastic TNBC.

Main Methods:

  • Scanning Electron Microscopy (SEM) for structural analysis.
  • Proteomics and RNA sequencing for protein and gene expression profiling.
  • Oscillating rheometry to measure ECM stiffness.

Main Results:

  • Metaplastic TNBC showed larger pore size and increased ECM stiffness compared to control adipose tissue.
  • Proteomic analysis revealed significant enrichment of ECM proteins, particularly glycoproteins.
  • Reduced expression of collagen COL3A1 was observed, with no change in COL1A1/COL1A2.
  • MFAP2 overexpression in metaplastic cells upregulated epithelial-to-mesenchymal transition genes.

Conclusions:

  • Metaplastic TNBC exhibits a distinct extracellular matrix signature and onco-architecture.
  • Altered ECM composition and stiffness contribute to the aggressive nature of metaplastic TNBC.
  • MFAP2 may play a role in promoting tumor progression via epithelial-to-mesenchymal transition.