Serological analysis of BALB/C methylcholanthrene sarcoma Meth A by SEREX: identification of a cancer/testis antigen

Int J Cancer. 2000 Dec 15;88(6):845-51. doi: 10.1002/1097-0215(20001215)88:6<845::aid-ijc1>3.0.co;2-n.

Abstract

Antigens of BALB/c methylcholanthrene-induced fibrosarcoma Meth A recognized by the host humoral immune response were investigated by serological analysis of antigens by recombinant expression cloning (SEREX). Immunoscreening a cDNA library from Meth A (Kgamma) cells (Meth A retrovirally transfected with murine IFN-gamma cDNA) with sera from BALB/c mice growing parental Meth A transplants identified 10 antigens. One of them, OY-MS-4, showed characteristics of a cancer/testis (CT) antigen. Nucleotide sequence analysis revealed that OY-MS-4 was identical to a mouse placenta and embryonic expression gene (pem) known to be selectively expressed during embryogenesis and in transformed cell lines. In adult mice, expression of OY-MS-4 was restricted to testis and placenta. Four of 6 methylcholanthrene-induced fibrosarcomas in BALB/c mice showed strong expression of OY-MS-4. In 6 T-cell leukemias, only a dimethylbenzanthracene-induced leukemia, EL4 (C57BL), showed strong expression. Two other tumors, A20.2J and P815, induced by ethylnitrosourea and methylcholanthrene, respectively, also strongly expressed OY-MS-4. The other 9 gene products identified in Meth A by SEREX were expressed in all 15 tumors tested and in a range of normal tissues. Sequence analysis of cDNA inserts coding for the SEREX-defined antigens showed no evidence of mutation. Despite the expression of OY-MS-1-10 antigens in methylcholanthrene sarcomas other than Meth A, no antibody was detected in the sera of mice bearing these other sarcomas. The basis for the unique immunogenicity of OY-MS-1-10 presented by Meth A, but not by other syngeneic tumors expressing these gene products, is unknown.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Neoplasm / immunology*
  • Antigen-Antibody Reactions
  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / genetics
  • Carcinogens
  • DNA, Complementary / genetics
  • Male
  • Methylcholanthrene
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma, Experimental / chemically induced
  • Sarcoma, Experimental / immunology*
  • Serologic Tests / methods*
  • Tumor Cells, Cultured / immunology

Substances

  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • Carcinogens
  • DNA, Complementary
  • RNA, Messenger
  • Methylcholanthrene