Original Paper

The expression of CXCR4, CXCL12 and CXCR7 in malignant pleural mesothelioma†

  1. Tong Li1,2,‡,
  2. Hui Li2,‡,
  3. Yucheng Wang3,
  4. Chansonette Harvard4,
  5. Jia-Li Tan5,6,
  6. Alfred Au7,
  7. Zhidong Xu1,
  8. David M Jablons1,*,
  9. Liang You1,*

Article first published online: 5 JAN 2011

DOI: 10.1002/path.2829

Issue

The Journal of Pathology

The Journal of Pathology

Volume 223, Issue 4, pages 519–530, March 2011

Additional Information

How to Cite

Li, T., Li, H., Wang, Y., Harvard, C., Tan, J.-L., Au, A., Xu, Z., Jablons, D. M. and You, L. (2011), The expression of CXCR4, CXCL12 and CXCR7 in malignant pleural mesothelioma. The Journal of Pathology, 223: 519–530. doi: 10.1002/path.2829

Author Information

  1. 1

    Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA

  2. 2

    Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital University of Medical Science, Beijing, 100020, PR China

  3. 3

    Department of Surgery, University of California, San Francisco, CA 94143, USA

  4. 4

    University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Canada

  5. 5

    Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, PR China

  6. 6

    Department of Orofacial Science, University of California, San Francisco, CA 94143, USA

  7. 7

    Tissue Core, Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA

  1. ‡

    These authors contributed equally to this work.

*Department of Surgery, UCSF Helen Diller Family Comprehensive Cancer, Center University of California, San Francisco, Campus Box 1724, 2340 Sutter Street, N221, San Francisco, CA 94143-1724, USA.

  1. †

    No conflicts of interest were declared.

Publication History

  1. Issue published online: 3 FEB 2011
  2. Article first published online: 5 JAN 2011
  3. Accepted manuscript online: 25 NOV 2010 09:48AM EST
  4. Manuscript Accepted: 22 NOV 2010
  5. Manuscript Revised: 6 NOV 2010
  6. Manuscript Received: 27 AUG 2010

Funded by

  • NIH. Grant Number: R01 CA140654-01A1

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Keywords:

  • mesothelioma;
  • CXCL12;
  • CXCR4;
  • CXCR7;
  • Akt

Abstract

The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, are involved in tumour progression, metastasis, and survival. We investigated the expression of CXCR4, CXCL12, and CXCR7 in malignant pleural mesothelioma to determine if they are possible biomarkers and potential therapeutic targets. Forty-one mesothelioma tumour tissues, ten normal human pleural tissues, and two mesothelioma cell lines were stained with anti-CXCR4, anti-CXCL12, anti-CXCR7, and anti-p-Akt antibodies. RT-PCR was performed to determine the expression of CXCR4, CXCL12, and CXCR7 in six human mesothelioma cell lines (H28, 211H, H2052, ms-1, H290, and H513) and one human normal mesothelial cell line, LP9. These seven cell lines were also stained with anti-CXCR7. We found that CXCR4 and CXCL12 were expressed in 97.6% and 78.0% mesothelioma tissue samples, concurrently with strong expression of p-Akt (R2 = 0.739 and 0.620, respectively). In addition, CXCR7 expression was weaker than CXCR4 expression in mesothelioma tissues. Furthermore, RT-PCR showed that CXCR4 and CXCL12 were overexpressed in 5/6 mesothelioma cell lines (211H, H2052, ms-1, H290, and H513), whereas CXCR7 was overexpressed in only 2/6 (H513 and H2052). Moreover, we found that the CXCR4 antagonist AMD3100 inhibited the growth of all five mesothelioma cell lines that overexpress CXCR4 and CXCL12. Our results suggest that the Akt–mTOR pathway is involved during the interruption of the CXCL12/CXCR4 axis in these five mesothelioma cell lines. In conclusion, CXCR4 and CXCL12 are highly expressed in most mesothelioma cell lines and tumour tissues, suggesting that CXCR4 and CXCL12 may be used as biomarkers for patients with mesothelioma. The CXCL12–CXCR4 interaction may be a potential therapeutic target for mesothelioma. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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