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@ARTICLE{Depner:119865,
author = {S. Depner$^*$ and W. Lederle and C. Gutschalk$^*$ and N.
Linde$^*$ and A. Zajonz$^*$ and M. M. Mueller$^*$},
title = {{C}ell type specific interleukin-6 induced responses in
tumor keratinocytes and stromal fibroblasts are essential
for invasive growth.},
journal = {International journal of cancer},
volume = {135},
number = {3},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2017-00460},
pages = {551-562},
year = {2014},
abstract = {Interleukin-6 (IL-6) is one of the major inflammatory
interleukins that has been linked to cancer progression. In
our model for human skin squamous cell carcinoma (SCC), IL-6
expression is strongly upregulated upon progression from
benign tumors to highly malignant, metastasizing SCCs. We
now demonstrate that IL-6 promotes malignant and invasive
tumor growth in human skin SCCs by inducing cell type
specific cytokine profiles in tumor keratinocytes and
stromal fibroblasts, activating the latter towards a tumor
associated fibroblast (TAF) phenotype. In three-dimensional
organotypic cocultures in vitro invasive growth of IL-6
overexpressing tumor keratinocytes, is associated with
increased expression of matrix metalloproteinase-2 (MMP-2),
MMP-14 and tissue inhibitor of metalloproteinases-2, and
clearly depends on IL-6 activated fibroblasts. IL-6-induced
secretion of monocyte chemotactic protein-1 (MCP-1) in tumor
keratinocytes and of hepatocyte growth factor in fibroblasts
is crucial for regulating expression and activation of
MMP-2. This functional role of IL-6 is confirmed in vivo.
Here MMP-14 and MMP-2 expression occur exclusively in
surface transplants of IL-6 overexpressing keratinocytes and
fibroblasts are identified as important source of MMP-2. Our
data indicate that tumor keratinocytes derived IL-6
activates stromal fibroblasts towards a TAF phenotype,
promoting tumor invasion via enhanced expression and
activation of MMP-2.},
keywords = {Culture Media, Conditioned (NLM Chemicals) / Interleukin-6
(NLM Chemicals) / MMP2 protein, human (NLM Chemicals) /
Matrix Metalloproteinase 2 (NLM Chemicals)},
cin = {A150},
ddc = {610},
cid = {I:(DE-He78)A150-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:23165423},
url = {https://inrepo02.dkfz.de/record/119865},
}