MDSC and TGF-β are required for facilitation of tumor growth in the lungs of mice exposed to carbon nanotubes
Published Date:Mar 05 2015
Source:Cancer Res. 75(8):1615-1623.
Mice, Inbred C57BL
Myeloid-derived Suppressor Cells
Single-walled Carbon Nanotubes
Transforming Growth Factor Beta
Pubmed Central ID:PMC4401633
Funding:R01 OH008282/OH/NIOSH CDC HHS/United States
R01ES019304/ES/NIEHS NIH HHS/United States
R01 CA154369/CA/NCI NIH HHS/United States
R01 ES019304/ES/NIEHS NIH HHS/United States
R01CA154369/CA/NCI NIH HHS/United States
Description: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.
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