World Trade Center Dust Exposure Promotes Cancer in PTEN-deficient Mouse Prostates

Author:

Wang Lin1,Xu Yitian2ORCID,Zhang Licheng2ORCID,Kang Kyeongah2ORCID,Kobryn Andriy1,Portman Kensey1,Gordon Ronald E3,Pan Ping-Ying2ORCID,Taioli Emanuela45ORCID,Aaronson Stuart A15,Chen Shu-Hsia12,Mulholland David J15ORCID

Affiliation:

1. 1Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

2. 2Center for Immunotherapy Research, Cancer Center of Excellence, Houston Methodist Research Institute, Houston, Texas.

3. 3Department of Pathology, Icahn School of Medicine, New York, New York.

4. 4Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York.

5. 5Tisch Cancer Institute, New York, New York.

Abstract

During the 9/11 attacks, individuals were exposed to World Trade Center (WTC) dust which contained a complex mixture of carcinogens. Epidemiologic studies have revealed the increased incidence of prostate and thyroid cancer in WTC survivors and responders. While reports have shown that WTC-dust associates with the increased prevalence of inflammatory-related disorders, studies to date have not determined whether this exposure impacts cancer progression. In this study, we have used genetically engineered mouse (GEM) models with prostate-specific deletion of the PTEN tumor suppressor to study the impact of WTC-dust exposure on deposition of dust particles, inflammation, and cancer progression. In normal C57/BL6 mice, dust exposure increased cellular expression of inflammatory genes with highest levels in the lung and peripheral blood. In normal and tumor-bearing GEM mice, increased immune cell infiltration to the lungs was observed. Pathologic evaluation of mice at different timepoints showed that WTC-dust exposure promoted PI3K-AKT activation, increased epithelial proliferation and acinar invasion in prostates with heterozygous and homozygous Pten loss. Using autochthonous and transplant GEM models of prostate cancer, we demonstrated that dust exposure caused reduced survival as compared with control cohorts. Finally, we used imaging mass cytometry to detect elevated immune cell infiltration and cellular expression of inflammatory markers in prostate tumors isolated from human WTC survivors. Collectively, our study shows that chronic inflammation, induced by WTC dust exposure, promotes more aggressive cancer in genetically predisposed prostates and potentially in patients. Significance: We provide the first evidence that exposure to WTC dust promotes prostate cancer progression. These data may impact the diagnoses, clinical management, and treatment of responders who have or will develop cancer.

Funder

HHS | CDC | National Institute for Occupational Safety and Health

Publisher

American Association for Cancer Research (AACR)

Reference59 articles.

1. Characterization of the dust/smoke aerosol that settled east of the World Trade Center (WTC) in lower Manhattan after the collapse of the WTC 11 September 2001;Lioy;Environ Health Perspect,2002

2. Biomonitoring of chemical exposure among New York City firefighters responding to the World Trade Center fire and collapse;Edelman;Environ Health Perspect,2003

3. Air levels of carcinogenic polycyclic aromatic hydrocarbons after the World Trade Center disaster;Pleil;Proc Natl Acad Sci U S A,2004

4. Cancer incidence in World Trade Center rescue and recovery workers: 14 years of follow-up;Li;J Natl Cancer Inst,2022

5. Temporal association of prostate cancer incidence with World Trade Center rescue/recovery work;Goldfarb;Occup Environ Med,2021

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3