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Long-term pulmonary exposure to multi-walled carbon nanotubes promotes breast cancer metastatic cascades

Nature Nanotechnology volume 14, pages 719–727 (2019)Cite this article

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Abstract

Anthropogenic carbon nanotubes, with a fibrous structure and physical properties similar to asbestos, have recently been found within human lung tissues. However, the reported carbon-nanotube-elicited pulmonary pathologies have been mostly confined to inflammatory or neoplastic lesions in the lungs or adjacent tissues. In the present study, we demonstrate that a single pulmonary exposure to multi-walled carbon nanotubes dramatically enhances angiogenesis and the invasiveness of orthotopically implanted mammary carcinoma, leading to metastasis and rapid colonization of the lungs and other organs. Exposure to multi-walled carbon nanotubes stimulates local and systemic inflammation, contributing to the formation of pre-metastatic and metastatic niches. Our study suggests that nanoscale-material-elicited pulmonary lesions may exert complex and extended influences on tumour progression. Given the increasing presence of carbon nanotubes in the environment, this report emphasizes the urgent need to escalate efforts assessing the long-term risks of airborne nanomaterial exposure in non-lung cancer progression.

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Fig. 1: Materials and experimental design.
Fig. 2: Pulmonary inflammation and fibrosis formation at day 120 after a single intratracheal instillation of MWCNTs.
Fig. 3: Assessment of primary breast tumours.
Fig. 4: Invasiveness of primary tumour cells derived from tumours in vivo.
Fig. 5: Evaluation of lung metastases of tumours.
Fig. 6: Positive feedback loop between VEGFA and COX-2 promotes cell invasion and metastasis.

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Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by the National Key R&D Program of China (2016YFC1302305, 2016YFA0201600, 2016YFE0133100), the National Natural Science Foundation of China (81672615, 815022829, 91543206, 31622026, 31700879), the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (11621505), the Shenzhen Development and Reform Commission Subject Construction Project [2017]1434, the Bureau of International Co-operation Chinese Academy of Sciences (GJHG1852) and the National Science Fund for Distinguished Young Scholars (11425520).

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Author notes

  1. These authors contributed equally: Xuefei Lu, Yong Zhu.

Authors and Affiliations

  1. Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Biomedical Engineering, Faculty of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China

    Xuefei Lu, Yong Zhu, Wenchang Qian, Leiyan Yang & Tao Zhu

  2. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China

    Ru Bai, Rong Cai, Ying Liu & Chunying Chen

  3. Department of Pathology, Anhui Medical University, Hefei, Anhui, China

    Zhengsheng Wu

  4. Department of Pathology, Anhui Provincial Cancer Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, China

    Hong Yan

  5. Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

    Tao Li

  6. Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, Guangdong, China

    Vijay Pandey & Peter E. Lobie

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Contributions

T.Z. and C.C. conceived the project and supervised the study. T.Z., C.C., X.L. and Y.Z. designed the experiments. X.L. and Y.Z. performed experiments with assistance from R.B., Z.W., W.Q., L.Y., R.C., H.Y., Y.L., T.L. and V.P.; X.L. and Y.Z. analysed the data. T.Z., C.C. and X.L. co-wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Chunying Chen or Tao Zhu.

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The authors declare no competing interests.

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Journal peer review information: Nature Nanotechnology thanks Wolfgang Kreyling, Iseult Lynch and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Lu, X., Zhu, Y., Bai, R. et al. Long-term pulmonary exposure to multi-walled carbon nanotubes promotes breast cancer metastatic cascades. Nat. Nanotechnol. 14, 719–727 (2019). https://doi.org/10.1038/s41565-019-0472-4

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