Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Significance of Expression of Human METCAM/MUC18 in Nasopharyngeal Carcinomas and Metastatic Lesions

  • Lin, Jin-Ching (Department of Radiation Oncology, Taichung Veterans General Hospital) ;
  • Chiang, Cheng-Feng (Department of Microbiology and Immunology, Emory University School of Medicine) ;
  • Wang, Shur-Wern (Department of Microbiology and Immunology, Emory University School of Medicine) ;
  • Wang, Wen-Yi (Department of Basic Medicine, Hung Kuang University) ;
  • Kwan, Po-Cheung (Department of Pathology, Taichung Veterans General Hospital) ;
  • Wu, Guang-Jer (Department of Microbiology and Immunology, Emory University School of Medicine)
  • Published : 2014.01.15
Download PDF
⟨ Previous Next ⟩

Abstract

Human METCAM/MUC18, a cell adhesion molecule (CAM) in the immunoglobulin-like gene super family, plays a dual role in the progression of several epithelium cancers; however, its role in the nasopharyngeal carcinoma (NPC) remains unclear. To initiate the study we determined human METCAM/MUC18 expression in tissue samples of normal nasopharynx (NP), NPCs, and metastatic lesions, and in two established NPC cell lines. Immunoblotting analysis was used for the determination in lysates of frozen tissues, and immunohistochemistry (IHC) for expression in formalin-fixed, paraffin-embedded tissue sections of 7 normal nasopharynx specimens, 94 NPC tissue specimens, and 3 metastatic lesions. Human METCAM/MUC18 was expressed in 100% of the normal NP, not expressed in 73% of NPC specimens (or expressed at very low levels in only about 27% of NPC specimens), and expressed again in all of the metastatic lesions. The level of human METCAM/MUC18 expression in NPC tissues was about one fifth of that in the normal NP and metastatic lesions. The low level of human METCAM/MUC18 expression in NPC specimens was confirmed by a weak signal of RT-PCR amplification of the mRNA. Low expression levels of human METCAM/MUC18 in NPC tissues were also reflected in the seven established NPC cell lines. These findings provided the first evidence that diminished expression of human METCAM/MUC18 is an indicator for the emergence of NPC, but increased expression then occurs with metastatic progression, suggesting that huMETCAM/MUC18, perhaps similar to TGF-${\beta}$, may be a tumor suppressor, but a metastasis promoter for NPC.

Keywords

References

  1. Ausubel FM, Brent R, Kingston RE, et al (1987). Current Protocols in Molecular Biology. New York: Green Publishing Associates and Wiley-Interscience Press; 4.9.
  2. Cavallaro U, Christofori G (2004). Cell adhesion and signaling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer, 4, 118-32. https://doi.org/10.1038/nrc1276
  3. Chiang CF, Son EL, Wu GJ (2005). Oral treatment of male TRAMP mice with doxazosin suppresses prostate tumor growth and metastasis. Prostate, 64, 408-18. https://doi.org/10.1002/pros.20260
  4. Chomczyuski P, Sacchi N (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate-phenolchloroform extraction. Anal Biochem, 162, 156-9.
  5. Craefor NPS, Hunter KW (2006) New perspectives on hereditary influences in metastatic progression. Trends in Genetics, 22, 555-61. https://doi.org/10.1016/j.tig.2006.07.009
  6. De The' G (1982). Epidemiology of Epstein-Barr virus and associated diseases. In: Roizman B, editor. The Herpesviruses. New York: Plenum Press; Vol 1, pp. 25-87.
  7. Hassen E, Farhat K, Gabbouj S, et al (2007). TAP1 gene polymorphisms and nasopharyngeal carcinoma risk in a Tunisian population. Cancer Genet Cytogenet, 175, 41-6. https://doi.org/10.1016/j.cancergencyto.2007.01.009
  8. Ho JHC (1972). Current knowledge of the epidemiology of nasopharyngeal carcinoma (NPC). In: Biggs P, de The' G, Payne L, eds. Oncogenesis and Herpesviruses. Lyon: IARC; pp. 357-66.
  9. Huang GW, Mo WN, Kuang GQ, et al (2001). Expression of p16, nm-23-H1, E-cadherin, and CD44 gene products and their significance in nasopharyngeal carcinomas. Laryngoscope, 111, 1465-71. https://doi.org/10.1097/00005537-200108000-00025
  10. Krishna SM, Kattoor J, Balaram P (2005). Down regulation of adhesion protein E-cadherin in Epstein-Barr virus infected nasopharyngeal carcinomas. Cancer Biomarker, 1, 271-7.
  11. Lee AWM, Ng WT, Chan YH, et al (2012). The battle against nasopharyngeal cancer. Radiother Oncol, 104, 272-278. https://doi.org/10.1016/j.radonc.2012.08.001
  12. Lehmann JM, Reithmuller G, Johnson JP (1989). MUC18, a marker of tumor progression in human melanoma. Proc Natl Acad Sci USA, 86, 9891-5. https://doi.org/10.1073/pnas.86.24.9891
  13. Li Q, Yu Y, Bischoff J, et al (2003). Differential expression of CD146 in tissues and endothelial cells derived from infantile haemangioma and normal human skin. J Pathology, 201, 296-302. https://doi.org/10.1002/path.1443
  14. Li Z, Ren Y, Lin SX, et al (2004). Association of E-cadherin and ${\beta}$-catenin with metastasis in nasopharyngeal carcinomas. Chin Med J, 117, 1232-9.
  15. Lin CT, Wong CI, Chan WY, et al (1990). Establishment and characterization of two nasopharyngeal carcinoma cell lines. Lab Invest, 62, 713-24.
  16. Lin CT, Chan WY, Chen W, et al (1993). Characterization of seven newly established nasopharyngeal carcinoma cell lines. Lab Invest, 68, 716-27.
  17. Lung HL, Cheng Y, Kumaran MK, et al (2004). Fine mapping of the 11Q22-23 tumor suppressive region and involvement of TSLC1 in nasopharyngeal carcinoma. Int J Cancer, 112, 628-35. https://doi.org/10.1002/ijc.20454
  18. Lung HL, Bangarusamy DK, Xie D, et al (2005). THY1 is a candidate tumor suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma. Oncogene, 24, 6525-32.
  19. McGary EC, Heimberger A, Mills L, et al (2003). A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vitro. Clin Cancer Res, 9, 6560-6.
  20. Raab-Traub N (1992). Epstein-Barr virus and nasopharyngeal carcinoma. Semin in Cancer Biol, 3, 297-307.
  21. Roberts AB, Wakefield LM (2003). The two faces of transforming growth factor beta (TGF-${\beta}$) in carcinogenesis. Proc Natl Acad Sci USA, 100, 8621-3. https://doi.org/10.1073/pnas.1633291100
  22. Schlagbauer-Wadl H, Jansen B, Muller M, et al (1999). Influence of MUC18/MCAM/CD146 expression on human melanoma growth and metastasis in SCID mice. Int J Cancer, 81, 951-5. https://doi.org/10.1002/(SICI)1097-0215(19990611)81:6<951::AID-IJC18>3.0.CO;2-V
  23. Shih IM (1999). The role of CD146 (Mel-CAM) in biology and pathology. J Pathol, 189, 4-11. https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<4::AID-PATH332>3.0.CO;2-P
  24. Tsai CN, Tsai CL, Tse KP, et al (2002). The Epstein-Barr virus oncogene product, latent membrane protein 1, induces the down-regulation of E-cadherin gene expression via activation of DNA methyltransferases. Proc Natl Acad Sci USA, 99, 10084-9. https://doi.org/10.1073/pnas.152059399
  25. Wei W, Sham JS (2005). Nasopharyngeal carcinoma. Lancet, 365, 2041-54. https://doi.org/10.1016/S0140-6736(05)66698-6
  26. Wei YS, Zhu YH, Du B, et al (2007). Association of transforming growth factor ${\beta}$1 gene polymorphisms with genetic susceptibility to nasopharyngeal carcinoma. Clin Chim Acta, 380, 165-9. https://doi.org/10.1016/j.cca.2007.02.008
  27. Wu GJ, Varma VA, Wu MWH, et al (2001a). Expression of a human cell adhesion molecule, MUC18, in prostate cancer cell lines and tissues. Prostate, 48, 305-15. https://doi.org/10.1002/pros.1111
  28. Wu GJ, Wu MWH, Wang SW, et al (2001b). Isolation and characterization of the major form of human MUC18 cDNA gene and correlation of MUC18 over-expression in prostate cancer cells and tissues with malignant progression. Gene, 279, 17-31. https://doi.org/10.1016/S0378-1119(01)00736-3
  29. Wu GJ (2004). The role of MUC18 in prostate carcinoma. In: Hayat MA, editor. Immunohistochemistry and in situ hybridization of human carcinoma. Vol 2. Molecular pathology, lung carcinoma, breast carcinoma, and prostate carcinoma. Amsterdam: Elsevier Science/Academic Press; pp. 347-58.
  30. Wu GJ, Peng Q, Fu P, et al (2004). Ectopic expression of human MUC18 increases metastasis of human prostate cancer cells. Gene, 327, 201-13. https://doi.org/10.1016/j.gene.2003.11.018
  31. Wu GJ (2005). METCAM/MUC18 expression and cancer metastasis. Curr Genomics, 6, 333-49. https://doi.org/10.2174/1389202054750211
  32. Wu GJ, Fu P, Chiang C, et al (2005). Increased expression of MUC18 correlates with the metastatic progression of mouse prostate adenocarcinoma in the TRAMP model. J Urology, 173, 1778-83. https://doi.org/10.1097/01.ju.0000154643.30048.2c
  33. Wu GJ, Fu P, Wang SW, et al (2008). Enforced expression of MCAM/MUC18 increases in vitro motility and invasiveness and in vivo metastasis of two mouse melanoma K1735 sublines in a syngeneic mouse model. Mol Cancer Res, 6, 1666-77. https://doi.org/10.1158/1541-7786.MCR-07-2200
  34. Wu GJ, Wu MWH, Liu Y (2011). Enforced expression of human METCAM/MUC18 increases the tumorigenesis of human prostate cancer cells in nude mice. J Urology, 185, 1504-12. https://doi.org/10.1016/j.juro.2010.11.052
  35. Wu GJ (2012). Dual roles of METCAM in the in the progression of different cancers. J Oncol, 2012, 853797.
  36. Xie S, Luca M, Huang S, et al (1997). Expression of MCAM/ MCU18 by human melanoma cells leads to increased tumor growth and metastasis. Cancer Res, 57, 2295-303.
  37. Yang H., Wang SW, Liu Z, et al (2011). Isolation and characterization of murine MUC18 cDNA gene, and correlation of MUC18 expression in murine melanoma cell lines with metastatic ability. Gene, 265, 133-45.
  38. Yi ZC, Wang H, Zhang GY, et al (2006). Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation. Oral Oncol, 43, 898-904.
  39. Yoshizaki T (2002). Promotion of metastasis in nasopharyngeal carcinoma by Epstein-Barr virus latent membrane protein-1. Histol Histopathol, 17, 845-50.
  40. Yu Y, Dong W, Zhou X, et al (2004). The significance of soluble intercellular adhesion molecule 1 (ICAM-1) and transformation growth factor alpha in patients with nasopharyngeal carcinomas. Acta Otolaryngol Head Neck Surg, 130, 1205-8. https://doi.org/10.1001/archotol.130.10.1205
  41. Zeng GF, Cai SX, Wu GJ (2011). Up-regulation of METCAM/ MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells. BMC Cancer, 11, 113. https://doi.org/10.1186/1471-2407-11-113
  42. Zeng GF, Cai SX, Liu Y, et al (2012a). METCAM/MUC18 augments migration, invasion, and tumorigenicity of human breast cancer SK-BR-3 cells. Gene, 492, 229-38. https://doi.org/10.1016/j.gene.2011.10.024
  43. Zeng Q, Li W, Lu D, et al (2012b). CD146, an epithelialmesenchymal transition inducer, is associated with triplenegative breast cancer. Proc Natl Acad Sci USA, 109, 1127-32. https://doi.org/10.1073/pnas.1111053108

Cited by

  1. Five miRNAs as Novel Diagnostic Biomarker Candidates for Primary Nasopharyngeal Carcinoma vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7575
  2. Glycididazole Sodium Combined with Radiochemotherapy for Locally Advanced Nasopharyngeal Carcinoma vol.15, pp.6, 2014, https://doi.org/10.7314/APJCP.2014.15.6.2641
  3. METCAM/MUC18 is a novel tumor and metastasis suppressor for the human ovarian cancer SKOV3 cells vol.16, pp.1, 2016, https://doi.org/10.1186/s12885-016-2181-9
  4. Ectopic expression of MCAM/MUC18 increases in vitro motility and invasiveness, but decreases in vivo tumorigenesis and metastasis of a mouse melanoma K1735-9 subline in a syngeneic mouse model vol.33, pp.8, 2016, https://doi.org/10.1007/s10585-016-9812-z
  5. Cancer metastasis: enactment of the script for human reproductive drama vol.17, pp.1, 2017, https://doi.org/10.1186/s12935-017-0421-y
  6. METCAM/MUC18 Decreases the Malignant Propensity of Human Ovarian Carcinoma Cells vol.19, pp.10, 2018, https://doi.org/10.3390/ijms19102976
  7. Gene expression analysis of Atlantic salmon gills reveals mucin 5 and interleukin 4/13 as key molecules during amoebic gill disease vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-32019-8