IL-6 promotes malignant growth of skin SCCs by regulating a network of autocrine and paracrine cytokines.

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 Cancer

authors

Lederle W,Depner S,Schnur S,Obermueller E,Catone N,Just A,Fusenig NE,Mueller MM

doi

10.1002/ijc.25621

subject

Has Abstract

pub_date

2011-06-15 00:00:00

pages

2803-14

issue

12

eissn

0020-7136

issn

1097-0215

journal_volume

128

pub_type

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