title: Inflammation amplifier, a new paradigm in cancer biology.
abstract: Tumor-associated inflammation can induce various molecules expressed from the tumors themselves or surrounding cells to create a microenvironment 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-κB 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-α, are strongly enriched in genes related to the amplifier. The inflammation amplifier is activated by the stimulation of cytokines, such as TNF-α, 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-α, 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.
authors.affiliation: Authors' Affiliations: JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University; and JST-CREST, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Atsumi
authors.forename: Rajeev
authors.initials: R
authors.lastname: Singh
authors.forename: Lavannya
authors.initials: L
authors.lastname: Sabharwal
authors.forename: Hidenori
authors.initials: H
authors.lastname: Bando
authors.forename: Jie
authors.initials: J
authors.lastname: Meng
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Arima
authors.forename: Moe
authors.initials: M
authors.lastname: Yamada
authors.forename: Masaya
authors.initials: M
authors.lastname: Harada
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Jiang
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamimura
authors.forename: Hideki
authors.initials: H
authors.lastname: Ogura
authors.forename: Toshio
authors.initials: T
authors.lastname: Hirano
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D059016:Tumor Microenvironment