The chemokine CXCL13 in lung cancers associated with environmental polycyclic aromatic hydrocarbons pollution

  1. Gui-Zhen Wang
  2. Xin Cheng
  3. Bo Zhou
  4. Zhe-Sheng Wen
  5. Yun-Chao Huang
  6. Hao-Bin Chen
  7. Gao-Feng Li
  8. Zhi-Liang Huang
  9. Yong-Chun Zhou
  10. Lin Feng
  11. Ming-Ming Wei
  12. Li-Wei Qu
  13. Yi Cao
  14. Guang-Biao Zhou  Is a corresponding author
  1. University of Chinese Academy of Sciences, China
  2. Sun Yat-Sen University, China
  3. Kunming Medical University, China
  4. The First People's Hospital of Qujing, China
  5. The People's Liberation Army General Hospital, China
  6. Chinese Academy of Sciences, China

Abstract

More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province the lung cancer incidence is among the highest in China attributed to smoky coal combustion-generated PAH pollution. Here we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen bezo(a)pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in cxcl13 or its receptor, cxcr5, abrogated BaP-induced lung cancer in mice, demonstrating CXCL13's critical role in PAH-induced lung carcinogenesis.

Article and author information

Author details

  1. Gui-Zhen Wang

    State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xin Cheng

    State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Bo Zhou

    State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Zhe-Sheng Wen

    Department of Thoracic Surgery, Cancer Center, Sun Yat-Sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yun-Chao Huang

    Department of Thoracic Surgery, Yunnan Tumor Hospital, Kunming Medical University, Kunming, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Hao-Bin Chen

    Department of Pathology, The First People's Hospital of Qujing, Qujing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Gao-Feng Li

    Department of Thoracic Surgery, Yunnan Tumor Hospital, Kunming Medical University, Kunming, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Zhi-Liang Huang

    Department of Thoracic Surgery, Cancer Center, Sun Yat-Sen University, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yong-Chun Zhou

    Department of Thoracic Surgery, Yunnan Tumor Hospital, Kunming Medical University, Kunming, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Lin Feng

    Department of Pathology, The People's Liberation Army General Hospital, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Ming-Ming Wei

    State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Li-Wei Qu

    State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Yi Cao

    Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Guang-Biao Zhou

    State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Beijing, China
    For correspondence
    gbzhou@ioz.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. David Barbie, Dana-Farber Cancer Institute, United States

Ethics

Animal experimentation: Animal studies were conducted according to protocols approved by the Animal Ethics Committee of the Institute of Zoology, Chinese Academy of Sciences, with the approval ID of AEC2010070202.

Human subjects: The study was approved by the local research ethics committees of all participating sites; all lung cancer samples were collected with informed consent.

Version history

  1. Received: June 13, 2015
  2. Accepted: November 4, 2015
  3. Accepted Manuscript published: November 13, 2015 (version 1)
  4. Version of Record published: February 9, 2016 (version 2)

Copyright

© 2015, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,549
    views
  • 820
    downloads
  • 58
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Gui-Zhen Wang
  2. Xin Cheng
  3. Bo Zhou
  4. Zhe-Sheng Wen
  5. Yun-Chao Huang
  6. Hao-Bin Chen
  7. Gao-Feng Li
  8. Zhi-Liang Huang
  9. Yong-Chun Zhou
  10. Lin Feng
  11. Ming-Ming Wei
  12. Li-Wei Qu
  13. Yi Cao
  14. Guang-Biao Zhou
(2015)
The chemokine CXCL13 in lung cancers associated with environmental polycyclic aromatic hydrocarbons pollution
eLife 4:e09419.
https://doi.org/10.7554/eLife.09419

Share this article

https://doi.org/10.7554/eLife.09419

Further reading

    1. Cancer Biology
    Célia Guérin, David Tulasne
    Review Article

    Tyrosine kinase inhibitors (TKI) directed against MET have been recently approved to treat advanced non-small cell lung cancer (NSCLC) harbouring activating MET mutations. This success is the consequence of a long characterization of MET mutations in cancers, which we propose to outline in this review. MET, a receptor tyrosine kinase (RTK), displays in a broad panel of cancers many deregulations liable to promote tumour progression. The first MET mutation was discovered in 1997, in hereditary papillary renal cancer (HPRC), providing the first direct link between MET mutations and cancer development. As in other RTKs, these mutations are located in the kinase domain, leading in most cases to ligand-independent MET activation. In 2014, novel MET mutations were identified in several advanced cancers, including lung cancers. These mutations alter splice sites of exon 14, causing in-frame exon 14 skipping and deletion of a regulatory domain. Because these mutations are not located in the kinase domain, they are original and their mode of action has yet to be fully elucidated. Less than five years after the discovery of such mutations, the efficacy of a MET TKI was evidenced in NSCLC patients displaying MET exon 14 skipping. Yet its use led to a resistance mechanism involving acquisition of novel and already characterized MET mutations. Furthermore, novel somatic MET mutations are constantly being discovered. The challenge is no longer to identify them but to characterize them in order to predict their transforming activity and their sensitivity or resistance to MET TKIs, in order to adapt treatment.

    1. Cancer Biology
    2. Genetics and Genomics
    Kevin Nuno, Armon Azizi ... Ravindra Majeti
    Research Article

    Relapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts and found that 40% of relapses occur without changes in driver mutations, suggesting that non-genetic mechanisms drive relapse in a large proportion of cases. We therefore characterized epigenetic patterns of AML relapse using 26 matched diagnosis-relapse samples with ATAC-seq. This analysis identified a relapse-specific chromatin accessibility signature for mutationally stable AML, suggesting that AML undergoes epigenetic evolution at relapse independent of mutational changes. Analysis of leukemia stem cell (LSC) chromatin changes at relapse indicated that this leukemic compartment underwent significantly less epigenetic evolution than non-LSCs, while epigenetic changes in non-LSCs reflected overall evolution of the bulk leukemia. Finally, we used single-cell ATAC-seq paired with mitochondrial sequencing (mtscATAC) to map clones from diagnosis into relapse along with their epigenetic features. We found that distinct mitochondrially-defined clones exhibit more similar chromatin accessibility at relapse relative to diagnosis, demonstrating convergent epigenetic evolution in relapsed AML. These results demonstrate that epigenetic evolution is a feature of relapsed AML and that convergent epigenetic evolution can occur following treatment with induction chemotherapy.