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

Details

• Journal Article:
  Cancer Research Communications
• Personal Author:
  Wang, Lin ; Xu, Yitian ; Zhang, Licheng ; Kang, Kyeongah ; Kobryn, Andriy ; Portman, Kensey ; Gordon, Ronald E. ; Pan, Ping-Ying ; Taioli, Emanuela ; Aaronson, Stuart A. ; Chen, Shu-Hsia ; Mulholland, David J.
• Description:
  During the 9/11 attacks individuals were exposed to World Trade Center (WTC) dust which contained a complex mixture of carcinogens. Epidemiological 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. Pathological evaluation of mice at different time points 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 to control cohorts. Finally, we used imaging mass cytometry (IMC) 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. [Description provided by NIOSH]
• Subjects:
  Animals Blood Carcinogens Dust Emergency Responders Environmental Exposure Epidemiology Laboratories Lung Lung Diseases Mice Neoplasms Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety September 11 Terrorist Attacks

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• Keywords:
  World Trade Center; WTC; Environmental exposure; Dusts; Dust exposure; Carcinogens; Epidemiology; Prostate cancer; Thyroid gland disorders; First responders; Emergency responders; Cancer; Animals; Laboratory animals; Models; Tumors; Particulates; Particulate dust; Lung; Lung disorders; Blood; Respiratory system disorders; Pulmonary system disorders
• Source:
  Cancer Res Commun 2022 Jun; 2(6):518-532
• ISSN:
  2767-9764
• Pubmed ID:
  35911788
• Pubmed Central ID:
  PMC9336209
• Document Type:
  Text
• Funding:
  U01 OH011328/OH/NIOSH CDC HHSUnited States/ ; U01OH011328/ACL/ACL HHSUnited States/
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2 ; OSHA Region 6 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  32 pdf pages
• Volume:
  2
• Issue:
  6
• NIOSHTIC Number:
  nn:20065745
• Contact Point Address:
  David J. Mulholland, Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029
• Email:
  david.mulholland@mssm.edu
• Federal Fiscal Year:
  2022
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Collection(s):
  National Institute for Occupational Safety and Health CDC Public Access
• Main Document Checksum:
  urn:sha-512:701de1d6262395b553b1203930e492003aff43e09e007d96d2b514200393eb29a47f09516451112a8b96b8107af544adf5b5d521cf6f600ac4e7f0735454d57f
• Download URL:
  https://stacks.cdc.gov/view/cdc/119842/cdc_119842_DS1.pdf
• File Type:
  [PDF - 2.36 MB ]