Interleukins 1 and 6 as Main Mediators of Inflammation and Cancer.
The idea of a potential link between cancer and inflammation was first proposed by R. Virchow in the nineteenth century. However, clear evidence regarding a key role of inflammation in oncogenesis appeared only during the last decade. Now the tumor microenvironment is commonly considered as an obligatory and significant component of almost all types of cancer, and the cells infiltrating such microenvironment are a source of inflammatory cytokines. Such cytokines play a key role in regulating inflammation during both normal immune response and developing cancer. In this review, we explore the role of two inflammatory cytokines interleukin 1 and interleukin 6 in cancer development. These cytokines have pleiotropic effects on various cell types in the tumor microenvironment, particularly being able to regulate pro-oncogenic transcription factors NF-κB and STAT3. For this reason, such cytokines influence key parameters of oncogenesis, increasing cell resistance to apoptosis, proliferation of cancer cells, angiogenesis, invasion and malignancy as well as the ability of tumor cells to respond to anticancer therapy. Here we summarize novel experimental data regarding mechanisms underlying the interaction between chronic inflammation and malignant neoplasms.
Fox Chase Cancer Center, Cancer Prevention and Control program, Philadelphia, PA, USA. Sergey.grivennikov@fccc.edu.
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Dmitrieva
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IP
Shilovskiy
M R
MR
Khaitov
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Grivennikov
D000818:Animals; D063646:Carcinogenesis; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D059016:Tumor Microenvironment
C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6