Carbon nanotubes promote lung tumor progression through the induction of cancer-associated fibroblasts and cancer stem-like cells

Details

• Personal Author:
  Issaragrisil S ; Luanpitpong S ; Rojanasakul Y ; Stueckle, Todd A. ; Wang L
• Description:
  Pulmonary exposure to carbon nanotubes (CNTs) has recently been shown to promote the growth and neoplastic progression of lung adenocarcinoma in animals, but the underlying mechanisms are unknown. Accumulating evidence suggests that cancer-associated fibroblasts (CAFs) may promote tumor growth by providing appropriate tumor microenvironment. In the present study we investigated whether CNTs can induce CAFs and whether these cells can promote tumor formation in a xenograft mouse model. We show that exposure of normal human lung fibroblasts (NHLFs) to physiological relevant concentrations of single-walled (SW) CNTs (0.08-0.15 microg/cm2) upregulated the expression of podoplanin, a known CAF marker of human lung adenocarcinoma, suggesting that SWCNTs can trigger NHLFs to initiate CAFs. Subcutaneous injection of the SWCNT-exposed NHLFs along with human lung carcinoma H460 cells in NSG mice resulted in a high rate of tumor formation compared with the coinjection of vehicle-exposed NHLFs and H460 cells, indicating the tumor-promoting effect of SWCNT-exposed NHLFs. The mechanism by which SWCNT-exposed fibroblasts promote tumor growth was shown to involve cancer stem cell (CSC) induction, as determined by tumor sphere formation and side population assays. Together, our study unveils a novel mechanism of CNT-promoted lung carcinoma through the acquisition of CAFs that regulate CSC formation. [Description provided by NIOSH]
• Subjects:
  Biological Assay Biomarkers Environmental Monitoring Lung Lung Diseases Neoplasms Nervous System Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

  More +
• Keywords:
  Adenocarcinomas Analytical-models Bioassays Cancer Carbon-compounds Carcinomas Cell-transformation Cellular-reactions Exposure-assessment Glycoproteins Lung-cancer Lung-cells Nanotechnology Neoplastic-agents Neoplastic-transformation Protein-synthesis Proteins Pulmonary-cancer Pulmonary-system Tumors

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045953
• Citation:
  Toxicologist 2015 Mar; 144(1):266
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e10b84e35e38b34f441b98de4c1189d08dec050c4e42d6d956a433833fd4d3d0e93f93ff4f02b5c9fe0362541c906d333f18f044ef07aa409f6d4908f4c8e806
• Download URL:
  https://stacks.cdc.gov/view/cdc/201161/cdc_201161_DS1.pdf
• File Type:
  [PDF - 218.41 KB ]