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

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 a breast cancer animal model, long-term exposure to carbon nanotubes promotes tumour invasiveness and metastasis through activation of local and systemic inflammation.

[1]  Ali Khademhosseini,et al.  Carbon-based nanomaterials: multifunctional materials for biomedical engineering. , 2013, ACS nano.

[2]  Vincent Castranova,et al.  Carbon nanotubes induce malignant transformation and tumorigenesis of human lung epithelial cells. , 2011, Nano letters.

[3]  F. Bertucci,et al.  Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. , 2009, Cancer research.

[4]  M. Andersen,et al.  Inhaled Carbon Nanotubes Reach the Sub-Pleural Tissue in Mice , 2009, Nature nanotechnology.

[5]  William D. Travis,et al.  Case Report: Lung Disease in World Trade Center Responders Exposed to Dust and Smoke: Carbon Nanotubes Found in the Lungs of World Trade Center Patients and Dust Samples , 2009, Environmental health perspectives.

[6]  Anna Shvedova,et al.  Cardiovascular Effects of Pulmonary Exposure to Single-Wall Carbon Nanotubes , 2006, Environmental health perspectives.

[7]  T. King,et al.  An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis. , 1989, The American review of respiratory disease.

[8]  Peng Wang,et al.  Multiwall carbon nanotubes mediate macrophage activation and promote pulmonary fibrosis through TGF-β/Smad signaling pathway. , 2013, Small.

[9]  Shuo Chen,et al.  High-power lithium batteries from functionalized carbon-nanotube electrodes. , 2010, Nature nanotechnology.

[10]  Srinivas Nagaraj,et al.  Myeloid-derived suppressor cells as regulators of the immune system , 2009, Nature Reviews Immunology.

[11]  R. Ramsay,et al.  New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis , 2015, Journal of Mammary Gland Biology and Neoplasia.

[12]  Dong Wang,et al.  Breast Cancer Stem Cells Transition between Epithelial and Mesenchymal States Reflective of their Normal Counterparts , 2013, Stem cell reports.

[13]  M. Duechler,et al.  How do Tumors Actively Escape from Host Immunosurveillance? , 2010, Archivum Immunologiae et Therapiae Experimentalis.

[14]  Heather R. Roberts,et al.  The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. , 2009, Carcinogenesis.

[15]  Dongmei Wu,et al.  Stat-6 signaling pathway and not Interleukin-1 mediates multi-walled carbon nanotube-induced lung fibrosis in mice: insights from an adverse outcome pathway framework , 2017, Particle and Fibre Toxicology.

[16]  R. Weinberg,et al.  A Perspective on Cancer Cell Metastasis , 2011, Science.

[17]  Yang Jin,et al.  Vascular endothelial growth factor promotes the expression of cyclooxygenase 2 and matrix metalloproteinases in Lewis lung carcinoma cells , 2012, Experimental and therapeutic medicine.

[18]  A. Star,et al.  MDSC and TGFβ Are Required for Facilitation of Tumor Growth in the Lungs of Mice Exposed to Carbon Nanotubes. , 2015, Cancer research.

[19]  D. Alloyeau,et al.  Anthropogenic Carbon Nanotubes Found in the Airways of Parisian Children , 2015, EBioMedicine.

[20]  H. S. Jung,et al.  Optimized THP-1 differentiation is required for the detection of responses to weak stimuli , 2007, Inflammation Research.

[21]  Craig A. Poland,et al.  Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. , 2008, Nature nanotechnology.

[22]  J. Pollard,et al.  Immune cell promotion of metastasis , 2015, Nature Reviews Immunology.

[23]  P. Wesseling,et al.  Micronodular transformation as a novel mechanism of VEGF-A-induced metastasis , 2007, Oncogene.

[24]  Liying Wang,et al.  Induction of cancer-associated fibroblast-like cells by carbon nanotubes dictates its tumorigenicity , 2016, Scientific Reports.

[25]  Ken Donaldson,et al.  Nanotoxicology: new insights into nanotubes. , 2009, Nature nanotechnology.

[26]  J. Balmes,et al.  Outdoor air pollution and asthma , 2014, The Lancet.

[27]  P. Tran,et al.  Carbon nanofibers and carbon nanotubes in regenerative medicine. , 2009, Advanced drug delivery reviews.

[28]  Gerhard Christofori,et al.  Distinct mechanisms of tumor invasion and metastasis. , 2007, Trends in molecular medicine.

[29]  Y. Liu,et al.  Understanding the toxicity of carbon nanotubes. , 2013, Accounts of chemical research.

[30]  J. Folkman Role of angiogenesis in tumor growth and metastasis. , 2002, Seminars in oncology.

[31]  Hiroyuki Tsuda,et al.  Multiwalled carbon nanotubes intratracheally instilled into the rat lung induce development of pleural malignant mesothelioma and lung tumors , 2016, Cancer science.

[32]  G. Bae,et al.  Exposure assessment of carbon nanotube manufacturing workplaces , 2010, Inhalation toxicology.

[33]  J. Kanno,et al.  Multi‐walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats , 2012, Cancer science.

[34]  Liying Wang,et al.  Carcinogenic Potential of High Aspect Ratio Carbon Nanomaterials. , 2016, Environmental science. Nano.

[35]  Vincent Castranova,et al.  INHALATION EXPOSURE TO CARBON NANOTUBES (CNT) AND CARBON NANOFIBERS (CNF): METHODOLOGY AND DOSIMETRY , 2015, Journal of toxicology and environmental health. Part B, Critical reviews.

[36]  Y. Liu,et al.  Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor , 2015, Nature Communications.

[37]  B. Zetter,et al.  The Contribution of Angiogenesis to the Process of Metastasis. , 2015, Cancer journal.

[38]  R. Baughman,et al.  Carbon Nanotubes: Present and Future Commercial Applications , 2013, Science.

[39]  Bethan Psaila,et al.  The metastatic niche: adapting the foreign soil , 2009, Nature Reviews Cancer.