| Full description or abstract |
We have previously developed methods for enriching tissue samples for their ECM protein content by taking advantage of the relative insolubility of the ECM, and we have used these techniques in conjunction with mass spectrometry-based proteomics to profile the matrisome, the complete collection of both core ECM and ECM-associated proteins, in several different cancers. Here we define and compare the ECM components of metastatic niches and how they differ among the specific secondary sites common in TNBC. For this purpose, we use as a model the MDA-MB-231 human TNBC cell line, originally derived from a patient pleural effusion (24), which is capable of metastasizing to the brain, lungs, liver and bone marrow in mouse xenografts. We identify which ECM proteins are commonly elevated at multiple different metastatic sites, and which are preferentially elevated in particular sites. We investigate how these specific ECM proteins, as well as the tumor matrix overall, are differentially produced by the tumor and stromal cells; in this paper, we use stromal to include all cells in the tumor that are not tumor cells. These comparisons did not simply identify the most elevated proteins in each tissue, but rather the proteins most significantly different in abundance in one tissue relative to all others. Separate analyses were conducted for tumor-cell-derived (human) and stroma-derived (mouse) proteins. In this study, we performed an unbiased, quantitative mass spectrometric survey of ECM proteins present in MDA-MB-231 breast cancer xenograft metastases to the brain, lungs, liver and bone marrow. This gene set lists the tumor-cell secreted matrisome proteins found in significantly higher abundance in TNBC brain metastasis niche compared to TNBC bone, liver and lung metastatic niches. |
