EGFR/Ras-induced CCL20 production modulates the tumour microenvironment

• DOI: 10.1038/s41416-020-0943-2
• Publication Date: 2020-06-29T23:08:43Z
• Authors: Andreas Hippe; Stephan Alexander...; Péter Oláh; Peter Arne Gerber; Anne Schorr; Stephan Seeliger; Stephanie Holtz; Katharina Jannasch; Andor Pivarcsi; Bettina Buhren; Holger Schrumpf; Andreas Kislat; Erich Bünemann; Martin Steinhoff; Jens Fischer; Sérgio A. Lira; Petra Boukamp; Peter Hevezi; Nikolas Hendrik S...; Thomas Hoffmann; Frauke Alves; Jonathan Sleeman; Thomas Bauer; Jörg Klufa; Nicole Amberg; Maria Sibilia; Albert Zlotnik; Anja Müller-Homey; Bernhard Homey
• Keywords: CCL20

Abstract Background The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which turn modulates microenvironment. Methods effects EGFR/Ras on expression and translation CCL20 were analysed large set epithelial cancer cell lines tissues by RT-qPCR ELISA vitro. production was verified immunohistochemistry different correlated with clinical data. endothelial migration tumour-associated vascularisation comprehensively chemotaxis assays vitro CCR6-deficient mice vivo. Results Tumours facilitate progression EGFR/Ras-induced CCL20. Expression tumours correlates advanced stage, increased lymph node metastasis decreased survival patients. Microvascular abundantly express specific receptor CCR6. CCR6 signalling angiogenesis. show significantly growth vascularisation. observed phenotype is dependent deficiency stromal but not within immune system. Conclusion We propose that axis CCL20–CCR6 represents novel promising target to interfere microenvironment, opens an innovative multimodal strategy for therapy.