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The expression of Dishevelled-3 and glutamine metabolism in malignant pleural mesothelioma
  1. Tong Li1,2,
  2. Sheng-Cai Hou2,
  3. Jian-Hua Mao3,
  4. Yu-Cheng Wang4,
  5. Xiao-Dan Lu5,6,
  6. Jia-Li Tan7,8,
  7. Bin You2,
  8. Yu-Ping Liu2,
  9. Jian Ni1,9,
  10. Alfred Au10,
  11. David M Jablons1,
  12. Zhidong Xu1,
  13. Liang You1
  1. 1Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, USA
  2. 2Thoracic Surgery Department, Beijing Chao-Yang Hospital, Capital University of Medical Science, Beijing, China
  3. 3Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, USA
  4. 4Department of Surgery, University of California, San Francisco, USA
  5. 5Institute of Genetics and Cytology, School of Life Science, Northeast Normal University, Changchun, China
  6. 6Bioengineering Therapeutic Sciences, University of California, San Francisco, USA
  7. 7Department of Stomatology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China
  8. 8Department of Orofacial Science, University of California, San Francisco, USA
  9. 9Depatment of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
  10. 10Tissue Core, Comprehensive Cancer Center, University of California, San Francisco, USA
  1. Correspondence to Dr Liang You, Department of Surgery, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, Campus Box 1724, 2340 Sutter Street, N221, San Francisco, CA 94143-1724, USA;{at}

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Malignant pleural mesothelioma (MPM) is a highly aggressive tumour.1 Biomarker information for MPM is lacking and could prove useful for understanding MPM metastasis and proliferation, and for providing potential targets for therapy. The Dishevelled (Dvl) family of proteins are membrane-proximal signalling intermediates in the Wnt pathway.2 Moreover, we previously found that the Wnt pathway is activated in mesothelioma through Dvl3 overexpression.3 Excitatory amino acid transporters (EAATs) are known to function as glutamate carriers.4 ,5 Among the EAATs, EAAT1 is a ubiquitous subtype. Glutamine synthetase (GS) is another important enzyme that plays a role in the metabolic pathway of glutamate.6 In this study, we evaluated the possible association among expression levels of Dvl3, EAAT1 and GS in MPM to determine possible biomarkers and therapeutic targets.

Clinical data were obtained from 39 patients with primary MPM between 1997 and 2009. The diagnosis of malignant mesothelioma was confirmed by a review of the pathology reports in all cases. We also used human mesothelioma cell lines H28, 211H, H2052, MS-1, H290, H513 and human normal mesothelial cell line LP9 in this research.

Thirty-eight mesothelioma samples (seven that included adjacent normal pleural tissues to serve as controls) were obtained from the patients who were mentioned above. Samples for one patient were not available for EAAT1 staining, …

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  • Funding The present work was supported by NIH grant R01 CA140654-01A1 (LY).

  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.