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

## TL;DR

This study examines the structure and protein composition of the extracellular matrix in metaplastic triple-negative breast cancer, revealing distinct features compared to normal tissue.

## Contribution

The study provides the first interdisciplinary analysis of ECM composition and architecture in metaplastic triple-negative breast cancer.

## Key findings

- SEM showed larger pore size in metaplastic TNBC tumors compared to control adipose tissue.
- Proteomic analysis revealed enrichment of ECM glycoproteins but no changes in COL1A1/A2 and reduced COL3A1.
- MFAP2 overexpression in cancer cells upregulated epithelial-to-mesenchymal transition-related genes.

## Abstract

Alterations in the tumor extracellular environment and matrix stiffness promote tumor progression. Furthermore, correlational studies have identified enrichment of extracellular matrix (ECM) proteins (glycoproteins, collagens) in breast tumors. Despite these findings, there has yet to be an interdisciplinary analysis of both ECM composition and structural architecture in rare breast tumors, such as metaplastic breast cancer. Here, we explored changes in ECM protein expression and architecture in a triple-negative breast cancer (TNBC) metaplastic tumor through SEM, proteomics, and RNA sequencing. SEM revealed that the tumor pore size was larger compared to the control adipose tissue. Oscillating rheometry demonstrated increased ECM stiffness in the tumor compared to the control adipose breast adipose. Proteomic analysis of the metaplastic TNBC tumor showed significant enrichment for ECM proteins, notably glycoproteins compared to the control adipose. Interestingly, these samples showed no observed changes in expression for major fibrillar collagens COL1A1 and COL1A2, and a reduced expression of COL3A1. To determine the impact of less characterized ECMs in metaplastic TNBC, we overexpressed MFAP2 in primary metaplastic breast cancer cells and performed RNA sequencing. MFAP2 overexpression was associated with upregulation of epithelial-to-mesenchymal transition-related genes. Overall, our results establish an extracellular signature and onco-architecture for the metaplastic triple-negative tumor type.