Utilizing Proteomics to Identify Extracellular Matrix Changes During Breast Cancer Metastasis

Breast cancer is one of the most commonly diagnosed cancers in women, with 1 in 8 women diagnosed during her lifetime. Distant metastatic breast cancer accounts for a majority of deaths in breast cancer patients. Changes in both the architecture and the biochemical composition of the extracellular matrix (ECM) occur during metastatic dissemination at both the primary tumor and the early metastatic niche. These changes play a significant role in the cell fate, and can alter proliferation, migration, and quiescence of cancer cells. This study utilizes tandem mass spectrometry to study ECM protein changes, specifically in the lungs, using an immune competent murine model of metastatic breast cancer. Liquid chromatography-tandem mass spectrometry was used to identify and quantify key ECM proteins in the primary tumors, lungs, and metastatic tumors during cancer progression. Fibronectin (FN) was upregulated in the primary tumor, suggestive of a more invasive mesenchymal-like cell. However, FN was decreased in abundance in metastatic tumors, which is favorable for a more epithelial phenotype, prompting tumor growth. The diseased lungs appear to have highly collagenous proteins, suggesting an increased stiffness in the matrix. This increase in stiffness would reduce physiologically induced strains, and potentially facilitate growth of metastatic lesions in the lungs. Characterization of the changes in the ECM during cancer progression will aid in development of future therapies as well as guide the design of relevant in vitro models, ultimately enhancing the knowledge of this phenomenon.