Deconstruction of a metastatic tumor microenvironment reveals a common matrix response in human cancersMore about Open Access at the Crick
Authors listOliver MT Pearce Robin Delaine-Smith Eleni Maniati Sam Nichols Jun Wang Steffen Böhm Vinothini Rajeeve Dayem Ullah Probir Chakravarty Roanne R Jones Anne Montfort Tom Dowe John Gribben J Louise Jones Hemant M Kocher Jonathan S Serody Benjamin G Vincent John Connelly James D Brenton Claude Chelala Pedro R Cutillas Michelle Lockley Conrad Bessant Martin M Knight Frances R Balkwill
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. Conducting multilevel analysis with data integration on biopsies with a range of disease involvement identifies important features of the evolving tumor microenvironment. The data suggest that despite the large spectrum of genomic alterations, some human malignancies may have a common and potentially targetable matrix response that influences the course of disease. .
Journal Cancer Discovery
Issue number 3