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

Cancer Res
Authors
Keywords
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. 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.

Year of Publication
2020
Journal
Cancer Res
Volume
80
Issue
7
Pages
1475-1485
Date Published
2020 04 01
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-19-2961
PubMed ID
32019869
PubMed Central ID
PMC7127975
Links
Grant list
P30 CA014051 / CA / NCI NIH HHS / United States
U01 CA214125 / CA / NCI NIH HHS / United States
U54 CA126515 / CA / NCI NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States
U24 CA210986 / CA / NCI NIH HHS / United States