Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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A comprehensive Analysis of a Large Panel of Cancer/Testis (CT) Antigens in Korea Breast Cancer

한국 유방암 환자에서 cancer/testis antigen의 발현분석

  • Bae, Jae-Ho (Departments of Biochemistry School of Medicine, Pusan National University) ;
  • Kim, Min-Ju (Departments of Biochemistry School of Medicine, Pusan National University) ;
  • Park, Hae-Rim (Departments of Biochemistry School of Medicine, Pusan National University) ;
  • Song, Myung-Ha (Departments of Biochemistry School of Medicine, Pusan National University) ;
  • Kim, Jee-Yeon (pathology) ;
  • Lee, Chang-Hun (pathology) ;
  • Kwak, Hi-Suk (Surgery) ;
  • Lee, Sang-Yull (Departments of Biochemistry School of Medicine, Pusan National University)
  • 배재호 (부산대학교 의학전문대학원 생화학교실) ;
  • 김민주 (부산대학교 의학전문대학원 생화학교실) ;
  • 박해림 (부산대학교 의학전문대학원 생화학교실) ;
  • 송명하 (부산대학교 의학전문대학원 생화학교실) ;
  • 김지연 (병리학교실) ;
  • 이창훈 (병리학교실) ;
  • 곽희숙 (외과학교실) ;
  • 이상률 (부산대학교 의학전문대학원 생화학교실)
  • Published : 2009.07.30
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Abstract

Cancer/testis (CT) antigens are immunogenic in cancer patients, exhibit highly tissue-restricted expression, and are considered promising target molecules for cancer vaccines. We investigated the expression of 13 CT genes in 29 Korean patients with primary breast carcinoma. The most frequently expressed CT genes were MAGE-3 (66%) and MAGE-1 (57%), followed by LAGE-1 (55%), NY-SAR-35 (49%), MAGE-4 (41%), NY-ESO-1 (38%), CT-7 (24%) and SSX-4 (24%), whereas SSX-1, SSX-2, MAGE-10 and NY-TLU-57 were found to be expressed significantly less often (3-7%) and SCP-l not all. Expression of at least one antigen was observed in 28 breast cancer samples. Immunohistochemistry was performed for NY-ESO-l and MAGE-3 protein expression in breast tumor samples. NY-ESO-l and MAGE-3 proteins were expressed in 11 of 29 (38%) and 12 of 29 (41 %) breast tumors. Our results suggest that CT antigens may be potential candidates for polyvalent immunotherapy in Korean breast cancer patients.

Cancer/testis(CT) antigens은 여러 종료의 암에서는 발현이 되지만, 정상조직에서는 고환에서만 발현이 되는 특이성을 가지고 있다. 이러한 특이성은 immunotherapy을 하기 위한 항암백신 개발에 매력적인 유전자로 알려져 있다. 본 연구에서는 29개의 한국유방암조직에서 13개의 CT antigens (NY-SAR35, SCP-1, SSX-1, SSX-2, SSX-4, MAGE-1, MAGE-3, MAGE-4, MAGE-10, CT-7, NY-TLU57, NY-ESO-1, and LAGE-1)의 발현빈도를 RT-PCR을 통하여 조사하고 환자의 임상학적 분류와 CT antigens의 발현빈도에 대하여 조사하였다. 29개의 유방암조직에 RT-PCR결과, 13개의 CT antigen중에 MAGE-3 (66%)와 MAGE-1(57%)에서 발현빈도가 가장 높았고 LAGE-1 (55%),NY-SAR-35 (49%),MAGE-4(41%), NY-ESO-1(38%), CT-7(24%), SSX-4(24%)순으로 발현빈도를 보였다. 그러나 SSX-1, SSX-2. MAGE-10와 NY-TLU-57의 발현은 3-7%로 매우 낮았고 특히 SCP-1는 발현되지 않았다. 29 유방암 조직에서 적어도 하나 이상의 CT antigen이 발현되는 샘플은 28(98%)이였다. 그러나 환자의 임상학적 분류와 CT antigens의 발현빈도와는 특징적인 관꼐가 없음을 알수있었다. 29개의 유방암조직에서 MAGE-3와 NY-ESO-1의 Protein level에서의 발현을 알아보기 위하여monoclonal antibody를 이용하여 면역조직염색을 하였다. MAGE-3은 29개 조직중에서 12개의 조직에서 발현되었으며 NY-ESO-1은 11개의 조직에서 발현되었다. 그러므로 CT antigens은 한국 유방암 조직에서 빈번하게 발현된 것을 알 수 있었으며 CT antigens을 기반으로 한 암 백신개발의 잠재적인 표적이 될 수 있을 것이라 사료된다.

Keywords

References

  1. Boel, P. C., M. L. Wildmann, R. Sensi, J. C. Brasseur, P. Renauld, T. Boon, and B. P. van der. 1995. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity 2, 167-175 https://doi.org/10.1016/S1074-7613(95)80053-0
  2. Chen, Q., H. Jackson, P. Parente, T. Luke, M. Rizkalla, T. Y. Tai, H. C. Zhu, N. A. Mifsud, N. Dimopoulos, K. A. Masterman, W. Hopkins, H. Goldie, E. Maraskovsky, S. Green, L. Miloradovic, J. McCluskey, L. J. Old, I. D. Davis, J. Cebon, and W. Chen. 2004. Immunodominant $CD4^{+}$ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant. Proc. Natl Acad. Sci. USA 101, 9363-9368 https://doi.org/10.1073/pnas.0403271101
  3. Greenlee, R. T., T. Murray, S. Bolden, and P. A. Wingo. 2000. Cancer statistics. CA Cancer J. Clin. 50, 7-33 https://doi.org/10.3322/canjclin.50.1.7
  4. Lee, S. Y. 2007. SEREX; discovery of tumor antigens. J. Life Science 17, 841-846 https://doi.org/10.5352/JLS.2007.17.6.841
  5. Lee, S. Y. , B. Williamson, O. L. Caballero, Y. T. Chen, M. J. Scanlan, G. Ritter, C. V. Jongeneel, A. J. Simpson, and L. J. Old. 2004. Identification of the gonad-specific anion transporter SLCO6A1 as a cancer/testis (CT) antigen expressed in human lung cancer. Cancer Immun. 17, 4-13
  6. Lee, S. Y., Y. Obata, M. Yoshida, E. Stockert, B. Williamson, A. Jungbluth, Y. T. Chen, L. J. Old, and M. J. Scanlan. 2003. Immunomic analysis of human sarcoma. Proc. Natl. Acad. Sci. USA 100, 2651-2656 https://doi.org/10.1073/pnas.0437972100
  7. Marchandab, M., C.J.A. Puntc, S. Aamdald, B. Escudiere, W.H.J. Kruitf, U. Keilholzg, L. Håkanssonh, N. van Barenab, Y. Humbletb, P. Muldersc, M.-F. Avrile, A. M. M. Eggermontf, C. Scheibenbogeng, J. Uitersi, J. Wandersi, M.Delirej, T. Boona, and G. Stoterf. 2003. Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report. Eur. J. Cancer 39, 70-77 https://doi.org/10.1016/S0959-8049(02)00479-3
  8. Mashino, K. N., F. Sadanaga, H. Tanaka, H. Yamaguchi, H. Nagashima, I. K. Sugimachi, and M. Mori. 2001. Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas. Br. J. Cancer 85, 713-720 https://doi.org/10.1054/bjoc.2001.1974
  9. Mischo, A., B. Kubuschok, K. Ertan, K. D. Preuss, B. Romeike, E. Regitz, C. Schormann,D. Bruijn, A. Wadle, F. Neumann, W. Schmidt, C. Renner, and M. Pfreundschuh. 2006. Prospective study on the expression of cancer testis genes and antibody responses in 100 consecutive patients with primary breast cancer. Intl. J. Cancer 118, 696-703 https://doi.org/10.1002/ijc.21352
  10. Rentzsch, C., S. Kayser, S. Stumm, I. Watermann, S. Walter, S. Stevanovic, D. Wallwiener, and B. Guckel. 2003. Evaluation of pre-existent immunity in patients with primary breast cancer: molecular and cellular assays to quantify antigen-specific T lymphocytes in peripheral blood mononuclear cells. Clin. Cancer Res. 9, 4376-4386
  11. Rimoldi, D., V. Rubio-Godoy, V. Dutoit, D. Lienard, S. Salvi, P. Guillaume, D. Speiser, E. Stockert, G. Spagnoli, C. Servis, J. C. Cerottini, F. Lejeune, P. Romero, and D. Valmori. 2000. Efficient simultaneous presentation of NY-ESO-1/LAGE-1 primary and nonprimary open reading frame-derived CTL epitopes in melanoma. J. Immunol. 165, 7253-7261 https://doi.org/10.4049/jimmunol.165.12.7253
  12. Russo, V., C. Traversari, A. Verrecchia, M. Mottolese, P. G. Natali, and C. Bordignon. 1995. Expression of the MAGE gene family in primary and metastatic human breast cancer: implications for tumor antigen-specific immunotherapy. Int. J. Cancer 64, 216-221 https://doi.org/10.1002/ijc.2910640313
  13. Scanlan, M. J., A. J. Simpson, and L. J. Old. 2004. The cancer/ testis genes: review, standardization, and commentary. Cancer Immun. 4, 1
  14. Seregni, E., A. Coli, and N. Mazzucca. 2004. Circulating tumour markers in breast cancer. Eur. J. Nucl. Med. Mol. Imaging 31 (Suppl 1), 15-22 https://doi.org/10.1007/s00259-004-1523-z
  15. Simpson, A. J., O. L. Caballero, A. Jungbluth, Y. T. Chen, and L. J. Old. 2005. Cancer/testis antigens, gametogenesis and cancer. Nat. Rev. Cancer 5, 615-625 https://doi.org/10.1038/nrc1669
  16. Slamon, D. J., B. Leyland-Jones, S. Shak, H. Fuchs, V. Paton, A. Bajamonde, T. Fleming, W. Eiermann, J. Wolte , M., Pegram, J. Baselga, and L. Norton. 2001. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783-792 https://doi.org/10.1056/NEJM200103153441101
  17. Van den Eynde, B., O. Peeters, O. De Backer, B. Gaugler, S. Lucas, and T. Boon. 1995. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J. Exp. Med. 182, 689-698 https://doi.org/10.1084/jem.182.3.689
  18. van der Bruggen, P., C. Traversari, P. Chomez, C. Lurquin, E. De Plaen, E. B. Van den, A. Knuth, and T. Boon. 1991. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254, 1643-1647 https://doi.org/10.1126/science.1840703
  19. Vaughan, H. A., S. Svobodova, D. SMacgregor D, S. Sturrock , A. A. Jungbluth, J. Browning, I. D. Davis, P. Parente, Y. T. Chen, E. Stockert, F. St Clair, L. J. Old, and J. Cebon. 2004. Immunohistochemical and molecular analysis of human melanomas for expression of the human cancer- testis antigens NY-ESO-1 and LAGE-1. Clin. Cancer Res. 10, 8396-8404 https://doi.org/10.1158/1078-0432.CCR-04-0809