Inflammation-Related IL1β/IL1R Signaling Promotes the Development of Asbestos-Induced Malignant Mesothelioma

被引：66

作者：

Kadariya, Yuwaraj ^{[1
]}

Menges, Craig W. ^{[1
]}

Talarchek, Jacqueline ^{[1
]}

Cai, Kathy Q. ^{[2
]}

Klein-Szanto, Andres J. ^{[1
,2
]}

Pietrofesa, Ralph A. ^{[3
]}

Christofidou-Solomidou, Melpo ^{[3
]}

Cheung, Mitchell ^{[1
]}

Mossman, Brooke T. ^{[4
]}

Shukla, Arti ^{[4
]}

Testa, Joseph R. ^{[1
]}

机构：

[1] Fox Chase Canc Ctr, Canc Biol Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA

[2] Fox Chase Canc Ctr, Histopathol Facil, 7701 Burholme Ave, Philadelphia, PA 19111 USA

[3] Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Perelman Sch Med, Philadelphia, PA 19104 USA

[4] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA

来源：

CANCER PREVENTION RESEARCH | 2016年 / 9卷 / 05期

关键词：

NECROSIS-FACTOR-ALPHA; CELL-PROLIFERATION; NALP3; INFLAMMASOME; DANGER SIGNALS; MURINE MODEL; TUMOR; CANCER; GENE; NF2; INTERLEUKIN-1-BETA;

D O I：

10.1158/1940-6207.CAPR-15-0347

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Exposure to asbestos is causally associated with the development of malignant mesothelioma, a cancer of cells lining the internal body cavities. Malignant mesothelioma is an aggressive cancer resistant to all current therapies. Once inhaled or ingested, asbestos causes inflammation in and around tissues that come in contact with these carcinogenic fibers. Recent studies suggest that inflammation is a major contributing factor in the development of many types of cancer, including malignant mesothelioma. The NALP3/NLRP3 inflammasome, including the component ASC, is thought to be an important mediator of inflammation in cells that sense extracellular insults, such as asbestos, and activate a signaling cascade resulting in release of mature IL1 beta and recruitment of inflammatory cells. To determine if inflammasome-mediated inflammation contributes to asbestos-induced malignant mesothelioma, we chronically exposed Asc-deficient mice and wildtype littermates to asbestos and evaluated differences in tumor incidence and latency. The Asc-deficient mice showed significantly delayed tumor onset and reduced malignant mesothelioma incidence compared with wild-type animals. We also tested whether inflammation-related release of IL1b contributes to tumor development in an accelerated mouse model of asbestos-induced malignant mesothelioma. Nf2(+/-); Cdkn2a(+/-) mice exposed to asbestos in the presence of anakinra, an IL1 receptor (IL1R) antagonist, showed a marked delay in the median time of malignant mesothelioma onset compared with similarly exposed mice given vehicle control (33.1 weeks vs. 22.6 weeks, respectively). Collectively, these studies provide evidence for a link between inflammation-related IL1 beta/IL1R signaling and the development of asbestos-induced malignant mesothelioma. Furthermore, these findings provide rationale for chemoprevention strategies targeting IL1 beta/IL1R signaling in high-risk, asbestos-exposed populations. (C) 2016 AACR.

引用

页码：406 / 414

页数：9

共 42 条

[11] The Nalp3 inflammasome is essential for the development of silicosis [J].

Cassel, Suzanne L. ;

Eisenbarth, Stephanie C. ;

Iyer, Shankar S. ;

Sadler, Jeffrey J. ;

Colegio, Oscar R. ;

Tephly, Linda A. ;

Carter, A. Brent ;

Rothman, Paul B. ;

Flavell, Richard A. ;

Sutterwala, Fayyaz S. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (26) :9035-9040

[12]

CHENG JQ, 1994, CANCER RES, V54, P5547

[13] NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma [J].

Chow, Melvyn T. ;

Tschopp, Juerg ;

Moeller, Andreas ;

Smyth, Mark J. .

IMMUNOLOGY AND CELL BIOLOGY, 2012, 90 (10) :983-986

[14] Concordance in diagnosis of mesotheliomas [J].

Davis, JM ;

Dungworth, DL ;

Boorman, GA .

TOXICOLOGIC PATHOLOGY, 1996, 24 (05) :662-663

[15] Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica [J].

Dostert, Catherine ;

Petrilli, Virginie ;

Van Bruggen, Robin ;

Steele, Chad ;

Mossman, Brooke T. ;

Tschopp, Jurg .

SCIENCE, 2008, 320 (5876) :674-677

[16] RECURRING LOSS INVOLVING CHROMOSOME-1, CHROMOSOME-3, AND CHROMOSOME-22 IN MALIGNANT MESOTHELIOMA - POSSIBLE SITES OF TUMOR SUPPRESSOR GENES [J].

FLEJTER, WL ;

LI, FP ;

ANTMAN, KH ;

TESTA, JR .

GENES CHROMOSOMES & CANCER, 1989, 1 (02) :148-154

[17] IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice [J].

Gasse, Pamela ;

Mary, Caroline ;

Guenon, Isabelle ;

Noulin, Nicolas ;

Charron, Sabine ;

Schnyder-Candrian, Silvia ;

Schnyder, Bruno ;

Akira, Shizuo ;

Quesniaux, Valerie F. J. ;

Lagente, Vincent ;

Ryffel, Bernhard ;

Couillin, Isabelle .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (12) :3786-3799

[18] The French National Mesothelioma Surveillance Program [J].

Goldberg, M. ;

Imbernon, E. ;

Rolland, P. ;

Ilg, A. Gilg Soit ;

Saves, M. ;

de Quillacq, A. ;

Frenay, C. ;

Chamming's, S. ;

Arveux, P. ;

Boutin, C. ;

Launoy, G. ;

Pairon, J. C. ;

Astoul, P. ;

Galateau-Salle, F. ;

Brochard, P. .

OCCUPATIONAL AND ENVIRONMENTAL MEDICINE, 2006, 63 (06) :390-395

[19] Mesothelioma incidence in 50 states and the District of Columbia, United States, 2003-2008 [J].

Henley, S. Jane ;

Larson, Theodore C. ;

Wu, Manxia ;

Antao, Vinicius C. S. ;

Lewis, Mary ;

Pinheiro, Germania A. ;

Eheman, Christie .

INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, 2013, 19 (01) :1-10

[20] Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells [J].

Hillegass, Jedd M. ;

Miller, Jill M. ;

MacPherson, Maximilian B. ;

Westbom, Catherine M. ;

Sayan, Mutlay ;

Thompson, Joyce K. ;

Macura, Sherrill L. ;

Perkins, Timothy N. ;

Beuschel, Stacie L. ;

Alexeeva, Vlada ;

Pass, Harvey I. ;

Steele, Chad ;

Mossman, Brooke T. ;

Shukla, Arti .

PARTICLE AND FIBRE TOXICOLOGY, 2013, 10 :1-14

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