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Breast tumors educate the proteome of stromal tissue in an individualized but coordinated manner

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Science Signaling  08 Aug 2017:
Vol. 10, Issue 491, eaam8065
DOI: 10.1126/scisignal.aam8065

Profiling the tumor stroma proteome

Communication between a tumor and cells in the surrounding stroma contributes to tumor growth, progression, and drug resistance. Thus, targeting this communication, in the primary tumor and especially in metastatic niches, may be an effective way to treat cancer. Wang et al. grew patient breast tumors subcutaneously in mice and obtained species-distinguished proteomic profiles of the tumors (human) and tumor-associated stroma (mouse). The authors found that all breast tumors consistently altered clustered subsets of the stromal proteome, particularly proteins involved in immune signaling, but that these varied in a subtype- and stage-specific manner. These findings may have future implications for treatment stratification and provide a platform from which to understand this experimental model and tumor-stroma interactions on a large-scale protein level.


Cancer forms specialized microenvironmental niches that promote local invasion and colonization. Engrafted patient-derived xenografts (PDXs) locally invade and colonize naïve stroma in mice while enabling unambiguous molecular discrimination of human proteins in the tumor from mouse proteins in the microenvironment. To characterize how patient breast tumors form a niche and educate naïve stroma, subcutaneous breast cancer PDXs were globally profiled by species-specific quantitative proteomics. Regulation of PDX stromal proteins by breast tumors was extensive, with 35% of the stromal proteome altered by tumors consistently across different animals and passages. Differentially regulated proteins in the stroma clustered into six signatures, which included both known and previously unappreciated contributors to tumor invasion and colonization. Stromal proteomes were coordinately regulated; however, the sets of proteins altered by each tumor were highly distinct. Integrated analysis of tumor and stromal proteins, a comparison made possible in these xenograft models, indicated that the known hallmarks of cancer contribute pleiotropically to establishing and maintaining the microenvironmental niche of the tumor. Education of the stroma by the tumor is therefore an intrinsic property of breast tumors that is highly individualized, yet proceeds by consistent, nonrandom, and defined tumor-promoting molecular alterations.

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