Deconstruction of a metastatic tumor microenvironment reveals a common matrix response in human cancers
Institution: Barts Cancer Institute, Queen Mary University of London; Francis Crick Institute
Corresponding Researcher: Frances Balkwill
Data Link(s): RNA-seq data have been deposited in Gene Expression Omnibus (GEO) under the accession number GSE71340. Proteomic data are available via the PRIDE database accession number PXD004060. All of the primary data are deposited at http://www.canbuild.org.uk.
Keyword(s): NA
Summary
We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we show how nonmalignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define, for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, while also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases. Although we studied a single metastatic site from one human malignancy, a pattern of expression of 22 matrisome genes distinguished patients with a shorter overall survival in ovarian and 12 other primary solid cancers, suggesting that there may be a common matrix response to human cancer.
