MDSC and TGFβ Are Required for Facilitation of Tumor Growth in the Lungs of Mice Exposed to Carbon Nanotubes.
During the last decades, changes have been observed in the frequency of different histologic 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 etiologic 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.
HELD, NIOSH, CDC, Morgantown, West Virginia. Department of Pharmacology and Physiology, West Virginia University, Morgantown, West Virginia. ats1@cdc.gov.
Anna A
AA
Shvedova
HELD, NIOSH, CDC, Morgantown, West Virginia.
Elena R
ER
Kisin
HELD, NIOSH, CDC, Morgantown, West Virginia.
Naveena
N
Yanamala
HELD, NIOSH, CDC, Morgantown, West Virginia.
Alexey V
AV
Tkach
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Dmitriy W
DW
Gutkin
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania.
Alexander
A
Star
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Galina V
GV
Shurin
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania. Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Valerian E
VE
Kagan
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Michael R
MR
Shurin
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D007108:Immune Tolerance; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000473:pathology / Q000502:physiology*; D037742:Nanotubes, Carbon / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D047368:Tumor Burden; D019139:Tumor Escape
D037742:Nanotubes, Carbon; D016212:Transforming Growth Factor beta