IL‐6 promotes malignant growth of skin SCCs by regulating a network of autocrine and paracrine cytokines |
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| Authors: | Sabine Schnur Eva Obermueller Nicola Catone Alexandra Just Norbert E. Fusenig Margareta M. Mueller |
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| Affiliation: | 1. Group Tumor and Microenvironment, DKFZ‐ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany;2. Translational Oncology Laboratory, Barts and the London Queen Marys School of Medicine and Dentistry, John Vane Science Centre, London, United Kingdom;3. Division of Carcinogenesis and Differentiation, German Cancer Research Center, Heidelberg, Germany |
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| 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. |
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| Keywords: | IL‐6 cytokine network MMP tumor progression |
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