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Proteomic Profiling of the ECM of Xenograft Breast Cancer Metastases in Different Organs Reveals Distinct Metastatic Niches
journal contributionposted on 11.11.2022, 21:16 authored by Jess D Hebert, Samuel A Myers, Alexandra NabaAlexandra Naba, Genevieve Abbruzzese, John M Lamar, Steven A Carr, Richard O Hynes
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.
CitationHebert, J. D., Myers, S. A., Naba, A., Abbruzzese, G., Lamar, J. M., Carr, S. A.Hynes, R. O. (2020). Proteomic Profiling of the ECM of Xenograft Breast Cancer Metastases in Different Organs Reveals Distinct Metastatic Niches. Cancer Research, 80(7), 1475-1485. https://doi.org/10.1158/0008-5472.can-19-2961
PublisherAmerican Association for Cancer Research (AACR)
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CancerBreast Cancer2.1 Biological and endogenous factorsBone MarrowBone Marrow NeoplasmsBrainBrain NeoplasmsCell SurvivalDisease ProgressionDown-RegulationExtracellular MatrixFemaleGene Expression ProfilingGene Knockdown TechniquesHumansLiverLiver NeoplasmsLungLung NeoplasmsNeoplastic Stem CellsProteomicsSerpinsStromal CellsTriple Negative Breast NeoplasmsTumor MicroenvironmentXenograft Model Antitumor AssaysOncology & CarcinogenesisOncology and Carcinogenesis