Tumor Biology

, Volume 35, Issue 4, pp 3185–3193 | Cite as

EMP1 inhibits nasopharyngeal cancer cell growth and metastasis through induction apoptosis and angiogenesis

  • G. G. Sun
  • Y. F. Lu
  • Z. Z. Fu
  • Y. J. Cheng
  • W. N. Hu
Research Article

Abstract

This study aimed to analyze the expression, clinical significance of epithelial membrane protein-1 (EMP1) in nasopharyngeal carcinoma, and the biological effect in its cell line by EMP1 overexpression. Immunohistochemistry and Western blot were used to analyze the EMP1 protein expression in 75 cases of nasopharyngeal cancer and 31 cases of normal tissues to study the relationship between EMP1 expression and clinical factors. Recombinant lentiviral vector was constructed to overexpress EMP1 and then infect nasopharyngeal cancer CNE2 cell line. Quantitative real-time RT-PCR and Western blot were used to detect the mRNA level and protein of EMP1. MTT assay, cell apoptosis, migration, and invasion assays were also conducted to determine the influence of the upregulated expression of EMP1 that might be found on CNE2 cells’ biological effect. Immunohistochemistry and Western blot: The level of EMP1 protein expression was found to be significantly lower in nasopharyngeal cancer tissue than in the normal tissues (P < 0.05). Decreased expression of EMP1 was significantly correlated with T stages, lymph node metastasis, clinic stage, and histological grade of patients with nasopharyngeal cancer (P < 0.05). Meanwhile, the loss of EMP1 expression correlated significantly with poor overall survival time by Kaplan–Meier analysis (P < 0.05). The result of biological function has shown that CNE2 cell-transfected EMP1 had a lower survival fraction, higher cell apoptosis, significant decrease in migration and invasion, higher caspase-9, and lower vascular endothelial growth factor C protein expression compared with CNE2 cell-untransfected EMP1 (P < 0.05). EMP1 expression decreased in nasopharyngeal cancer and correlated significantly T stages, lymph node metastasis, clinic stage, histological grade, and poor overall survival, suggesting that EMP1 may play important roles as a negative regulator to nasopharyngeal cancer cell.

Keywords

EMP1 Nasopharyngeal carcinoma Caspase-9 VEGF-C Metastasis Prognosis 

Notes

Conflicts of interest

None

References

  1. 1.
    Lo KW, To KF, Huang DP. Focus on nasopharyngeal carcinoma. Cancer Cell. 2004;5:423–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet. 2005;365:2041–54.PubMedCrossRefGoogle Scholar
  3. 3.
    Lai S, Wang G, Cao X, Li Z, Hu J, Wang J. EMP-1 promotes tumorigenesis of NSCLC through PI3K/AKT pathway. J Huazhong Univ Sci Technolog Med Sci. 2012;32:834–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Sobin LH, Fleming ID. TNM classification of malignant tumors, 5th ed. Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer. 1997;80:1803–4.Google Scholar
  5. 5.
    Taylor V, Welcher AA, Program AE, Suter U. Epithelial membrane protein-1, peripheral myelin protein 22, and lens membrane protein 20 define a novel gene family. J Biol Chem. 1995;270:28824–33.PubMedCrossRefGoogle Scholar
  6. 6.
    Lobsiger CS, Magyar JP, Taylor V, Wulf P, Welcher AA, Program AE, et al. Identification and characterization of a cDNA and the structural gene encoding the mouse epithelial membrane protein-1. Genomics. 1996;36:379–87.PubMedCrossRefGoogle Scholar
  7. 7.
    Wulf P, Suter U. Embryonic expression of epithelial membrane protein 1 in early neurons. Brain Res Dev Brain Res. 1999;116:169–80.PubMedCrossRefGoogle Scholar
  8. 8.
    Zoidl G, Blass-Kampmann S, D’Urso D, Schmalenbach C, Müller HW. Retroviral-mediated gene transfer of the peripheral myelin protein PMP22 in Schwann cells: modulation of cell growth. EMBO J. 1995;14:1122–8.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Jetten AM, Suter U. The peripheral myelin protein 22 and epithelial membrane protein family. Prog Nucleic Acid Res Mol Biol. 2000;64:97–129.PubMedCrossRefGoogle Scholar
  10. 10.
    Lee HS, Sherley JL, Chen JJ, Chiu CC, Chiou LL, Liang JD, et al. EMP1 is a junctional protein in a liver stem cell line and in the liver. Biochem Biophys Res Commun. 2005;334:996–1003.PubMedCrossRefGoogle Scholar
  11. 11.
    Gnirke AU, Weidle UH. Investigation of prevalence and regulation of expression of progression associated protein (PAP). Anticancer Res. 1998;18:4363–9.PubMedGoogle Scholar
  12. 12.
    Wang HT, Kong JP, Ding F, et al. Analysis of gene expression profile induced by EMP-1 in esophageal cancer cells using cDNA microarray. World J Gastroenterol. 2003;9:392–8.PubMedGoogle Scholar
  13. 13.
    Zhang J, Cao W, Xu Q, Chen WT. The expression of EMP1 is downregulated in oral squamous cell carcinoma and possibly associated with tumour metastasis. J Clin Pathol. 2011;64:25–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Liao Q, Guo X, Li X, Xiong W, Li X, Yang J, et al. Prohibitin is an important biomarker for nasopharyngeal carcinoma progression and prognosis. Eur J Cancer Prev. 2013;22:68–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhou JY, Chong VF, Khoo JB, Chan KL, Huang J. The relationship between nasopharyngeal carcinoma tumor volume and TNM T-classification: a quantitative analysis. Eur Arch Otorhinolaryngol. 2007;264:169–74.PubMedCrossRefGoogle Scholar
  16. 16.
    Wu Z, Zeng RF, Su Y, Gu MF, Huang SM. Prognostic significance of tumor volume in patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation therapy. Head Neck. 2013;35:689–94.PubMedCrossRefGoogle Scholar
  17. 17.
    Fu L, Chen W, Guo W, Wang J, Tian Y, Shi D, et al. Berberine targets AP-2/hTERT, NF-κB/COX-2, HIF-1α/VEGF and cytochrome-c/caspase signaling to suppress human cancer cell growth. PLoS One. 2013;8:e69240.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Sen S, Kawahara B, Chaudhuri G. Mitochondrial-associated nitric oxide synthase activity inhibits cytochrome c oxidase: implications for breast cancer. Free Radic Biol Med. 2013;57:210–20.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang JM, Wang HC, Wang HX, Ruan LH, Zhang YM, Li JT, et al. Oxidative stress and activities of caspase-8, -9, and -3 are involved in cryopreservation-induced apoptosis in granulosa cells. Eur J Obstet Gynecol Reprod Biol. 2013;166:52–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Peng J, Shao N, Peng H, Chen LQ. Prognostic significance of vascular endothelial growth factor expression in esophageal carcinoma: a meta-analysis. J Buon. 2013;18:398–406.PubMedGoogle Scholar
  21. 21.
    Xie LX, Zhai TT, Yang LP, Yang E, Zhang XH, Chen JY, et al. Lymphangiogenesis and prognostic significance of vascular endothelial growth factor C in gastro-oesophageal junction adenocarcinoma. Int J Exp Pathol. 2013;94:39–46.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • G. G. Sun
    • 1
  • Y. F. Lu
    • 2
  • Z. Z. Fu
    • 3
  • Y. J. Cheng
    • 4
  • W. N. Hu
    • 1
  1. 1.Department of ChemoradiotherapyTangshan People’s HospitalTangshanChina
  2. 2.Department of EndocrinologyTangshan Workers HospitalTangshanChina
  3. 3.Department of TumorThe First Hospital of QinhuangdaoQinhuangdaoChina
  4. 4.Department of RadiotherapyThe Fourth Hospital of Hebei Medical UniversityShijiazhuangChina

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