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Cancer Res DOI:10.1158/0008-5472.CAN-19-2961

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

Publication TypeJournal Article
Year of Publication2020
AuthorsHebert, JD, Myers, SA, Naba, A, Abbruzzese, G, Lamar, JM, Carr, SA, Hynes, RO
JournalCancer Res
Date Published2020 Apr 01

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.


Alternate JournalCancer Res.
PubMed ID32019869
PubMed Central IDPMC7127975
Grant ListT32 GM007287 / GM / NIGMS NIH HHS / United States
U24 CA210986 / CA / NCI NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
U01 CA214125 / CA / NCI NIH HHS / United States
U54 CA126515 / CA / NCI NIH HHS / United States