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.
Pharmacology, Toxicology and Pharmaceutical Science
1
3%
Computer Science
1
3%
Other
1
3%
Unknown
10
30%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 November 2012.
All research outputs
#20,656,820
of 25,374,647 outputs
Outputs from International Journal of Cancer
#10,870
of 12,204 outputs
Outputs of similar age
#174,224
of 235,803 outputs
Outputs of similar age from International Journal of Cancer
#96
of 124 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,204 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 5th percentile – i.e., 5% of its peers scored the same or lower than it.
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We're also able to compare this research output to 124 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.
