MDSC and TGFbeta are required for facilitation of tumor growth in the lungs of mice exposed to carbon nanotubes

Details

• Personal Author:
  Gutkin DW ; Kagan VE ; Kisin ER ; Shurin GV ; Shurin MR ; Shvedova AA ; Star A ; Tkach AV ; Yanamala N
• Description:
  During last decades, changes have been observed in the frequency of different histological subtypes of lung cancer, one of the most common causes of morbidity and mortality, with a declining proportion of squamous cell carcinomas and an increasing proportion of adenocarcinomas, particularly in developed countries. This suggests the emergence of new etiological factors and mechanisms including those defining the lung microenvironment, promoting tumor growth. Assuming that the lung is the main portal of entry for broadly used nanomaterials and their established proinflammatory propensities, we hypothesized that nanomaterials may contribute to changes facilitating tumor growth. Here, we report that an acute exposure to single-walled carbon nanotubes (SWCNT) induces recruitment and accumulation of lung-associated myeloid-derived suppressor cells (MDSC) and MDSC-derived production of TGFβ, resulting in upregulated tumor burden in the lung. The production of TGFβ by MDSC requires their interaction with both SWCNT and tumor cells. We conclude that pulmonary exposure to SWCNT favors the formation of a niche that supports ingrowth of lung carcinoma in vivo via activation of TGFβ production by SWCNT-attracted and -presensitized MDSC. [Description provided by NIOSH]
• Subjects:
  Laboratories Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Adenocarcinomas Author Keywords: Lung Carcinoma Cell Metabolism Cellular Function Cellular Reactions Etiology Laboratory Animals Lung Cancer Myeloid-derived Suppressor Cells Nanomaterials Nanotechnology Premalignant Niche Single-walled Carbon Nanotubes Transforming Growth Factor β Tumors

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• ISSN:
  0008-5472
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  75
• Issue:
  8
• NIOSHTIC Number:
  nn:20046011
• Citation:
  Cancer Res 2015 Apr; 75(8):1615-1623
• Contact Point Address:
  Dr. Anna A. Shvedova, CDC/NIOSH, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  ats1@cdc.gov
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Mining ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Cancer Research
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fef4b53d770ccf090b239740ac445e1a43b77bcc7a45a64979b05f1c65097c27791c8fe3f9e818e14f525a20bf71dc1012753a6e807e42f2507af36934634922
• Download URL:
  https://stacks.cdc.gov/view/cdc/201204/cdc_201204_DS1.pdf
• File Type:
  [PDF - 1.43 MB ]