Proteomic Profiling of the ECM of Xenograft Breast Cancer Metastases in Different Organs Reveals Distinct Metastatic Niches
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2020
- Source ID
- 10.1158/0008-5472.can-19-2961
Entities
People
- Alexandra Naba
- Genevieve Abbruzzese
- Janine S A Warren
- Jess D Hebert
- Richard O. Hynes
- Samuel A. Myers
- Steven A Carr
Organizations
- Howard Hughes Medical Institute
- Massachusetts Institute of Technology
- National Institutes of Health