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

ABSTRACT: 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.

INSTRUMENT(S): QExactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Mus Musculus (ncbitaxon:10090)

SUBMITTER: Steven A. Carr  

PROVIDER: MSV000084023 | MassIVE | Fri Jun 28 10:10:00 BST 2019

REPOSITORIES: MassIVE