Abstract:
:Cytokines play a crucial role in tumor initiation and progression. Here, we demonstrate that interleukin (IL)-6 is a key factor by driving tumor progression from benign to malignant, invasive tumors in the HaCaT-model of human skin carcinoma. IL-6 activates STAT3 and directly stimulates proliferation and migration of the benign noninvasive HaCaT-ras A-5 cells in vitro. Furthermore, IL-6 induces a complex, reciprocally regulated cytokine network in the tumor cells that includes inflammatory and angiogenic factors such as IL-8, GM-CSF, VEGF and MCP-1. These IL-6 effects lead to tumor cell invasion in organotypic cultures in vitro and to the formation of malignant and invasive s.c. tumors in vivo. Tumor invasion is supported by the IL-6 induced overexpression of MMP-1 in vitro and in vivo. These data demonstrate a key function of IL-6 in the progression of skin SCCs by regulating a complex cytokine and protease network and suggest new therapeutic approaches to target this central player in skin carcinogenesis.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Lederle W,Depner S,Schnur S,Obermueller E,Catone N,Just A,Fusenig NE,Mueller MMdoi
10.1002/ijc.25621subject
Has Abstractpub_date
2011-06-15 00:00:00pages
2803-14issue
12eissn
0020-7136issn
1097-0215journal_volume
128pub_type
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