MDSC and TGFβ Are Required for Facilitation of Tumor Growth in the Lungs of Mice Exposed to Carbon Nanotubes
| Autor: | Dmitriy W. Gutkin, Galina V. Shurin, Naveena Yanamala, Alexander Star, Anna A. Shvedova, Elena R. Kisin, Alexey V. Tkach, Michael R. Shurin, Valerian E. Kagan |
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| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Lung Neoplasms Adenocarcinoma Article Immune tolerance Mice Transforming Growth Factor beta Immune Tolerance medicine Animals Myeloid Cells Lung cancer Cells Cultured Cell Proliferation Mice Knockout Lung biology Nanotubes Carbon Chemistry Cell growth Transforming growth factor beta medicine.disease Tumor Burden Mice Inbred C57BL medicine.anatomical_structure Oncology Immunology biology.protein Myeloid-derived Suppressor Cell Tumor Escape Transforming growth factor |
| Zdroj: | Cancer Research. 75:1615-1623 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-14-2376 |
| Popis: | 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. Cancer Res; 75(8); 1615–23. ©2015 AACR. |
| Databáze: | OpenAIRE |
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