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

Our plain-English summary of Long-term pulmonary exposure to multi-walled carbon nanotubes promotes breast cancer metastatic cascades, by X. Lu, Y. Zhu, R. Bai, et al (Nature Nanotechnology, 2019).

The study

• Authors: X. Lu, Y. Zhu, R. Bai, Z. Wu, W. Qian, L. Yang, R. Cai, H. Yan, T. Li, V. Pandey, Y. Liu, P.E. Lobie, C. Chen, T. Zhu
• Journal: Nature Nanotechnology
• Published: 2019;14(7):719-727
• Cited by: 124 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This was a laboratory experiment in mice, with added cell-culture work. It tested multi-walled carbon nanotubes (MWCNTs), not asbestos. The authors describe these fibers as similar to asbestos in structure. Female BALB/c mice received a single dose of 60 μg of MWCNTs, or a salt-solution control, into the lungs through the windpipe. At 120 days, exposed mice had lung inflammation, granulomatous lesions and fibrosis, with no significant change in general health. Mouse breast cancer cells were then implanted in five mice per group. Tumour growth did not differ between groups, but tumours in exposed mice showed more blood-vessel formation and more local invasion. After the tumours were removed, imaging at day 4 showed strong lung signals in three of five exposed mice and none of the controls. At days 8 and 12, all five exposed mice showed strong signals, compared with a marginally detectable signal in two of five controls. The authors concluded that lung exposure to carbon nanotubes may represent a major long-term risk for breast cancer progression in people who work in carbon nanotube workplaces or laboratories.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment (mouse breast cancer model) with supporting cell-culture experiments
• Who was studied: Female BALB/c mice, 8 weeks old, about 20 g, from Shanghai. There were 20 or 21 per group. At 120 days, 15 control and 16 exposed mice were killed to examine the lungs, and 5 mice per group received implanted 4T1 mouse breast cancer cells. Mouse and human cell lines were also used.
• Exposure: A single dose of commercial multi-walled carbon nanotubes (MWCNTs), 20 to 50 μm long, at 60 μg per mouse. The dose was suspended in PBS (a salt solution) and given into the lungs through the windpipe (non-surgical intratracheal instillation). Controls received PBS alone. No asbestos was tested.
• Main results:
  • 120 days after the single dose, MWCNT-exposed mice had chronic lung inflammation and fibrosis.
  • MWCNT exposure did not significantly change general health (body weight, blood counts, blood chemistry).
  • Growth of the implanted breast tumours did not differ between exposed and control mice.
  • Tumours in exposed mice showed more blood-vessel formation (angiogenesis).
  • Tumours in exposed mice showed more local spread of cancer cells into the adjacent skin layer (dermis).
  • Four days after tumour removal, strong lung signals were seen in 3 of 5 exposed mice and in none of the control mice.
  • At days 8 and 12, strong lung signals were seen in all 5 exposed mice.
  • At days 8 and 12, only a marginally detectable signal was seen in 2 of the 5 control mice.
  • Microscope examination of the lungs showed a higher incidence of lung metastasis in the exposed group.
  • Small metastases were seen in the liver and in the capsule of the spleen in one exposed mouse.
  • Tumour cells grown from exposed mice formed 1.8-fold more first-generation and 2.5-fold more second-generation tumourspheres (clusters linked to cancer stem cells) than cells from control mice.
  • In those same tumour cells, ALDH-positive cancer stem cells were enriched sixfold in the exposed group.
  • In cell experiments, the authors reported that two proteins, VEGFA and COX-2, depended on each other and formed a feedback loop that regulated how invasive the cancer cells were.
• The authors' conclusion: The authors concluded that lung exposure to carbon nanotubes may represent a major long-term risk for breast cancer progression, especially invasion and metastasis, for people who work in carbon nanotube workplaces or laboratories.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Angiogenesis, Carcinoma, Metastasis, Inflammation, Lung Cancer.

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• Carboxylated short single-walled carbon nanotubes but not plain and multi-walled short carbon nanotubes show in vitro genotoxicity — M. Mrakovcic, C. Meindl, et al. (2015)
• Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons — A.A. Shvedova, N. Yanamala, et al. (2014)
• Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice — J.G. Teeguarden, B.J. Webb-Robertson, et al. (2011)
• A Single Aspiration of Rod-like Carbon Nanotubes Induces Asbestos-like Pulmonary Inflammation Mediated in Part by the IL-1 Receptor — E.M. Rydman, M. Ilves, et al. (2015)

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