MassIVE MSV000084023

Partial Public

Proteomic profiling of the ECM of breast cancer metastases in different organs reveals distinct metastatic niches

Description

Hebert JD, Myers SA, Naba A, Abbruzzese G, Lamar J, Carr SA, Hynes RO.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. We show that tumor and stromal cells cooperate in forming niches, with stromal cells producing predominantly core, structural ECM proteins and tumor cells producing a diverse array of ECM-associated proteins, including secreted factors and modulators of the matrix. Additionally, tumor and stromal cells together create distinct niches in each tissue, and we show that knocking down 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. [doi:10.25345/C5KD2P] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: extracellular matrix ; metastasis ; TMT10 ; Breast Cancer ; organotropism

Contact

Principal Investigators:
(in alphabetical order)
Steven A. Carr, Broad Institute of MIT and Harvard, United States
Submitting User: clauser
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