Inflammation Amplifier, a New Paradigm in Cancer Biology

被引：180

作者：

Atsumi, Toru ^{[1
,2
]}

Singh, Rajeev ^{[1
,2
]}

Sabharwal, Lavannya ^{[1
,2
]}

Bando, Hidenori ^{[1
,2
]}

Meng, Jie ^{[1
,2
]}

Arima, Yasunobu ^{[1
,2
]}

Yamada, Moe ^{[1
,2
]}

Harada, Masaya ^{[1
,2
]}

Jiang, Jing-Jing ^{[1
,2
]}

Kamimura, Daisuke ^{[1
,2
]}

Ogura, Hideki ^{[1
,2
]}

Hirano, Toshio ^{[3
]}

Murakami, Masaaki ^{[1
,2
]}

机构：

[1] Osaka Univ, Grad Sch Med, Grad Sch Frontier Biosci, JST CREST, Suita, Osaka 5650871, Japan

[2] Osaka Univ, WPI Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan

[3] JST CREST, Osaka, Japan

来源：

CANCER RESEARCH | 2014年 / 74卷 / 01期

基金：

日本科学技术振兴机构;

关键词：

POSITIVE-FEEDBACK; IL-6; AMPLIFIER; CELL; INTERLEUKIN-6; VEGF; OVEREXPRESSION; INSTABILITY; ACTIVATION; GROWTH; LINKS;

D O I：

10.1158/0008-5472.CAN-13-2322

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor-associated inflammation can induce various molecules expressed from the tumors themselves or surrounding cells to create a micro environment that potentially promotes cancer development. Inflammation, particularly chronic inflammation, is often linked to cancer development, even though its evolutionary role should impair nonself objects including tumors. The inflammation amplifier, a hyperinducer of chemokines in nonimmune cells, is the principal machinery for inflammation and is activated by the simultaneous stimulation of NF-kappa B and STAT3. We have redefined inflammation as local activation of the inflammation amplifier, which causes an accumulation of various immune cells followed by dysregulation of local homeostasis. Genes related to the inflammation amplifier have been genetically associated with various human inflammatory diseases. Here, we describe how cancer-associated genes, including interleukin (IL)-6, Ptgs2, ErbB1, Gas1, Serpine1, cMyc, and Vegf-alpha, are strongly enriched in genes related to the amplifier. The inflammation amplifier is activated by the stimulation of cytokines, such as TNF-alpha, IL-17, and IL-6, resulting in the subsequent expression of various target genes for chemokines and tumor-related genes like BCL2L11, CPNE7, FAS, HIF1-alpha, IL-1RAP, and SOD2. Thus, we conclude that inflammation does indeed associate with the development of cancer. The identified genes associated with the inflammation amplifier may thus make potential therapeutic targets of cancers. (C)2013 AACR.

引用

页码：8 / 14

页数：7

共 30 条

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