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National Academy of Sciences, Proceedings of the National Academy of Sciences, 6(116), p. 2237-2242, 2019

DOI: 10.1073/pnas.1820459116

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Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma

Journal article published in 2019 by Eva A. Ebbing, Amber P. van der Zalm, Anne Steins, Aafke Creemers ORCID, Simone Hermsen, Rosa Rentenaar, Michelle Klein, Cynthia Waasdorp, Gerrit K. J. Hooijer ORCID, Sybren L. Meijer, Kausilia K. Krishnadath, Cornelis J. A. Punt, Mark I. van Berge Henegouwen, Suzanne S. Gisbertz, Otto M. van Delden and other authors.
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Significance We found that cancer-associated fibroblasts, the most abundant noncancer cell type in esophageal cancer tissue, contribute to the resistance of tumors against currently applicable treatments. These cancer-associated fibroblasts do so by producing and secreting IL-6. IL-6 induces a mesenchymal, resistant tumor cell state. Inhibition of IL-6 reverted the mesenchymal cell state and resensitized tumor cells to therapy. Serum-borne proxies for the presence of IL-6–producing fibroblasts were identified and found to be predictive for the response to neoadjuvant therapy.