Proteomic Profiling of the ECM of Xenograft Breast Cancer Metastases in Different Organs Reveals Distinct Metastatic Niches

• Published in: Cancer research (Chicago, Ill.) Ill.), 2020-04, Vol.80 (7), p.1475-1485
• Main Authors: Hebert, Jess D, Myers, Samuel A, Naba, Alexandra, Abbruzzese, Genevieve, Lamar, John M, Carr, Steven A, Hynes, Richard O
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-19-2961

Metastasis causes most cancer-related deaths, and one poorly understood aspect of metastatic cancer is the adaptability of cells from a primary tumor to create new niches and survive in multiple, different secondary sites. We used quantitative mass spectrometry to analyze the extracellular matrix (ECM), a critical component of metastatic niches, in metastases to the brain, lungs, liver, and bone marrow, all derived from parental MDA-MB-231 triple-negative breast cancer cells. Tumor and stromal cells cooperated in forming niches; stromal cells produced predominantly core, structural ECM proteins and tumor cells produced a diverse array of ECM-associated proteins, including secreted factors and modulators of the matrix. In addition, tumor and stromal cells together created distinct niches in each tissue. Downregulation of SERPINB1, a protein elevated in brain metastases, led to a reduction in brain metastasis, suggesting that some niche-specific ECM proteins may be involved in metastatic tropism. SIGNIFICANCE: Tumor and stromal cells together create distinct ECM niches in breast cancer metastases to various tissues, providing new insight into how tumor cells adapt to survive in different tissue environments.