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IL‐6 promotes malignant growth of skin SCCs by regulating a network of autocrine and paracrine cytokines
Author(s) -
Lederle Wiltrud,
Depner Sofia,
Schnur Sabine,
Obermueller Eva,
Catone Nicola,
Just Alexandra,
Fusenig Norbert E.,
Mueller Margareta M.
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25621
Subject(s) - paracrine signalling , autocrine signalling , cancer research , cytokine , hacat , angiogenesis , carcinogenesis , tumor progression , biology , in vivo , in vitro , immunology , pathology , cancer , medicine , cell culture , receptor , biochemistry , microbiology and biotechnology , genetics
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.