Editors' ChoiceCancer

New connections: Understanding the tumor through the stroma

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Sci. Signal.  08 Aug 2017:
Vol. 10, Issue 491, eaao5803
DOI: 10.1126/scisignal.aao5803

Evaluating changes in the tumor stroma at the protein and signaling levels may uncover effective therapeutic targets for cancer patients.

Genomic profiling of tumors is a popular and increasingly cost-effective method for detecting cancer “drivers” and directing treatment strategies, but as well as being unable to detect protein-level changes (such as posttranscriptional activation), this approach in isolation misses information about the tumor microenvironment that may be critical to therapeutic success (see Ferrarelli and Gough). Two articles published in Science Signaling highlight efforts to explore not only the changes that occur in the protein landscape of the tumors but also those that occur in the protein profiles of the tumor microenvironment. In this issue, Wang et al. profiled the tumor stroma proteome. The authors grew patient-derived 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 implications for treatment stratification, and they provide a platform from which to understand this experimental model and tumor-stroma interactions on a large-scale protein level. In the Archives, Ostalecki et al. mapped the protein drivers of melanoma and their effects on surrounding keratinocytes. Using multiepitope ligand cartography on human skin samples, the authors identified changes in protein abundance and subcellular localization in melanocytes and keratinocytes that were associated with various stages of melanoma development. The findings revealed the transfer of a peptidase-metalloproteinase pair from early-stage BRAF-mutant/PTEN-null melanoma cells to adjacent normal keratinocytes through cell-cell contact. The recipient keratinocytes exhibited altered protein abundance and secretion. Together, these findings contribute to the exploration of the intercellular communication between the tumor and the stroma and how it might be therapeutically targeted in cancer patients.

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