Langerhans Cells Facilitate Epithelial DNA Damage and Squamous Cell Carcinoma

被引：96

作者：

Modi, Badri G. ^{[1
]}

Neustadter, Jason ^{[1
]}

Binda, Elisa ^{[9
,10
]}

Lewis, Julia ^{[1
]}

Filler, Renata B. ^{[1
]}

Roberts, Scott J. ^{[1
]}

Kwong, Bernice Y. ^{[1
]}

Reddy, Swapna ^{[1
]}

Overton, John D. ^{[3
,4
]}

Galan, Anjela ^{[1
]}

Tigelaar, Robert ^{[1
]}

Cai, Lining ^{[5
]}

Fu, Peter ^{[6
]}

Shlomchik, Mark ^{[2
]}

Kaplan, Daniel H. ^{[7
,8
]}

Hayday, Adrian ^{[9
,10
]}

Girardi, Michael ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Lab Med & Immunobiol, New Haven, CT 06520 USA

[3] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA

[4] Yale Univ, Sch Med, Yale Ctr Genome Anal, New Haven, CT 06520 USA

[5] Biotranex, Monmouth Jct, NJ 08852 USA

[6] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA

[7] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA

[8] Univ Minnesota, Dept Immunobiol, Minneapolis, MN 55455 USA

[9] Kings Coll London, Guys & St Thomas Hosp, Peter Gorer Dept Immunobiol, Comprehens Biomed Res Ctr, London SE1 9RT, England

[10] Canc Res UK CRUK, London Res Inst, London WC2 A, England

来源：

SCIENCE | 2012年 / 335卷 / 6064期

基金：

英国惠康基金;

关键词：

ARYL-HYDROCARBON RECEPTOR; CONTACT HYPERSENSITIVITY; MOUSE SKIN; T-CELLS; RAS GENE; H-RAS; MICE; CARCINOGENESIS; 7,12-DIMETHYLBENZ(A)ANTHRACENE; EXPRESSION;

D O I：

10.1126/science.1211600

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Polyaromatic hydrocarbons (PAHs) are prevalent, potent carcinogens, and 7,12-dimethylbenz[a]anthracene (DMBA) is a model PAH widely used to study tumorigenesis. Mice lacking Langerhans cells (LCs), a signatory epidermal dendritic cell (DC), are protected from cutaneous chemical carcinogenesis, independent of T cell immunity. Investigation of the underlying mechanism revealed that LC-deficient skin was relatively resistant to DMBA-induced DNA damage. LCs efficiently metabolized DMBA to DMBA-trans-3,4-diol, an intermediate proximal to oncogenic Hras mutation, and DMBA-treated LC-deficient skin contained significantly fewer Hras mutations. Moreover, DMBA-trans-3,4-diol application bypassed tumor resistance in LC-deficient mice. Additionally, the genotoxic impact of DMBA on human keratinocytes was significantly increased by prior incubation with human-derived LC. Thus, tissue-associated DC can enhance chemical carcinogenesis via PAH metabolism, highlighting the complex relation between immune cells and carcinogenesis.

引用

页码：104 / 108

页数：5

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