Proteomic Profiling of the ECM of Xenograft Breast Cancer Metastases in Different Organs Reveals Distinct Metastatic Niches
Name
nihms-1558781.pdf
Description
Accepted version
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2 MB
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Author(s)
Hebert, Jess D.
Myers, Samuel A.
Naba, Alexandra
Abbruzzese, Genevieve
Lamar, John M.
Carr, Steven A.
Hynes, Richard O.
Date Issued
February 2020
Journal
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Version
Author's final manuscript
Abstract
© 2020 American Association for Cancer Research. 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1158/0008-5472.can-19-2961
