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 dev...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2015-04, Vol.75 (8), p.1615-1623
Main Authors: Shvedova, Anna A, Kisin, Elena R, Yanamala, Naveena, Tkach, Alexey V, Gutkin, Dmitriy W, Star, Alexander, Shurin, Galina V, Kagan, Valerian E, Shurin, Michael R
Format: Article
Language:English
Subjects:
Adenocarcinoma - immunology
Adenocarcinoma - pathology
Animals
Cell Proliferation
Cells, Cultured
Immune Tolerance
Lung Neoplasms - immunology
Lung Neoplasms - pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Cells - pathology
Myeloid Cells - physiology
Nanotubes, Carbon - toxicity
Transforming Growth Factor beta - physiology
Tumor Burden
Tumor Escape
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-14-2376