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| Home > Publications database > Cell type specific interleukin-6 induced responses in tumor keratinocytes and stromal fibroblasts are essential for invasive growth. > print |
| 001 | 119865 | ||
| 005 | 20240228134957.0 | ||
| 024 | 7 | _ | |a pmid:23165423 |2 pmid |
| 024 | 7 | _ | |a 0020-7136 |2 ISSN |
| 024 | 7 | _ | |a 1097-0215 |2 ISSN |
| 024 | 7 | _ | |a altmetric:1080494 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2017-00460 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Depner, Sofia |0 P:(DE-He78)d6da8152e37bbf1d9843a7a213d99a30 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Cell type specific interleukin-6 induced responses in tumor keratinocytes and stromal fibroblasts are essential for invasive growth. |
| 260 | _ | _ | |a Bognor Regis |c 2014 |b Wiley-Liss |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1490183674_25954 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
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| 588 | _ | _ | |a Dataset connected to PubMed, |
| 650 | _ | 7 | |a Culture Media, Conditioned |2 NLM Chemicals |
| 650 | _ | 7 | |a Interleukin-6 |2 NLM Chemicals |
| 650 | _ | 7 | |a MMP2 protein, human |0 EC 3.4.24.24 |2 NLM Chemicals |
| 650 | _ | 7 | |a Matrix Metalloproteinase 2 |0 EC 3.4.24.24 |2 NLM Chemicals |
| 700 | 1 | _ | |a Lederle, Wiltrud |b 1 |
| 700 | 1 | _ | |a Gutschalk, Claudia |0 P:(DE-HGF)0 |b 2 |
| 700 | 1 | _ | |a Linde, Nina |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Zajonz, Alexandra |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Mueller, Margareta M |0 P:(DE-HGF)0 |b 5 |e Last author |
| 773 | _ | _ | |g Vol. 135, no. 3 |0 PERI:(DE-600)1474822-8 |n 3 |p 551-562 |t International journal of cancer |v 135 |y 2014 |x 0020-7136 |
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