Biopolym. Cell. 2003; 19(6):541-547.
Biomedicine
Identification of tumor-associated antigens in human thyroid papillar carcinoma
1Rodnin N. V., 1Tykhonkova I. O., 1Kyyamova R. G., 1Garifulin O. M., 1, 2Gout I. T., 1Filonenko V. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Ludwig Institute for Cancer Research
    91 Riding house str., London, UK, WIP8BT

Abstract

In this study two cDNA expressing libraries generated from thyroid papillar carcinomas were screened using SEREX approach. Thirty positive cDNA clones representing seventeen different genes were identified from both libraries. It is important to note, that three of them were isolated previously by other laboratories in SEREX screens of various types of human cancer. These include transcription factor NZF, a-catenin and BAG RP11 — a protein with unknown function. Moreover, we identified a whole panel of novel potential tumor-associated antigens, which would be further investigated. We are particularly interested in more detailed analysis of cathepsin H and transducer of ErbB2 (TOB2), which are differentially expressed in various types of human cancer. We will analyse the frequency of autoantibodies against identified antigens in sera of patients with various malignancies and healthy donors by heterologous screening. It is expected that among the clones isolated in this study, there might be novel cancer-associated markers.

References

[1] Schmutzler C, Koehrle J. Innovative strategies for the treatment of thyroid cancer. Eur J Endocrinol. 2000;143(1):15-24. PMID:10870026
[2] Nagataki S, Nystr?m E. Epidemiology and primary prevention of thyroid cancer. Thyroid. 2002;12(10):889-96.
[3] Parmiani G. Tumor immunity as autoimmunity: tumor antigens include normal self proteins which stimulate anergic peripheral T cells. Immunol Today. 1993;14(11):536-8.
[4] Old LJ, Chen YT. New paths in human cancer serology. J Exp Med. 1998;187(8):1163-7.
[5] J?ger D, Unkelbach M, Frei C, Bert F, Scanlan MJ, J?ger E, Old LJ, Chen YT, Knuth A. Identification of tumor-restricted antigens NY-BR-1, SCP-1, and a new cancer/testis-like antigen NW-BR-3 by serological screening of a testicular library with breast cancer serum. Cancer Immun. 2002;2:5.
[6] Behrends U, Schneider I, R?ssler S, Frauenknecht H, Golbeck A, Lechner B, Eigenstetter G, Zobywalski C, M?ller-Weihrich S, Graubner U, Schmid I, Sackerer D, Sp?th M, Goetz C, Prantl F, Asmuss HP, Bise K, Mautner J. Novel tumor antigens identified by autologous antibody screening of childhood medulloblastoma cDNA libraries. Int J Cancer. 2003;106(2):244-51.
[7] Scanlan MJ, J?ger D. Challenges to the development of antigen-specific breast cancer vaccines. Breast Cancer Res. 2001;3(2):95-8.
[8] Rodnin NV, Tykhonkova IO, Nemazany IO, Gorlova LM, Komissarenko IV, Palchevskiy SS, Kuharenko OP, Drobot LB, Matsuka GH, Filonenko VV, Gout IT. Serological identification of autoimmune reactive antigens in human thyroid cancer cells. Experimental Oncology. 2000; 22(3):135-8.
[9] Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156-9.
[10] Rodnin MV, Tykhonkova IO, Filonenko VV, Drobot LB, Matsuka GK, Gout IT. Search and characterization of melanoma antigens with the use of serological identification of antigens by recombinant expression cloning. Biopolym. Cell. 2000; 16 (5):339-44.
[11] Hajra KM, Fearon ER. Cadherin and catenin alterations in human cancer. Genes Chromosomes Cancer. 2002;34(3):255-68.
[12] Van Aken E, De Wever O, Correia da Rocha AS, Mareel M. Defective E-cadherin/catenin complexes in human cancer. Virchows Arch. 2001;439(6):725-51.
[13] Shiozaki H, Iihara K, Oka H, Kadowaki T, Matsui S, Gofuku J, Inoue M, Nagafuchi A, Tsukita S, Mori T. Immunohistochemical detection of alpha-catenin expression in human cancers. Am J Pathol. 1994;144(4):667-74.
[14] Soda G, Antonaci A, Bosco D, Nardoni S, Melis M. Expression of bcl-2, c-erbB-2, p53, and p21 (waf1-cip1) protein in thyroid carcinomas. J Exp Clin Cancer Res. 1999;18(3):363-7.
[15] Lee MS, Igawa T, Yuan TC, Zhang XQ, Lin FF, Lin MF. ErbB-2 signaling is involved in regulating PSA secretion in androgen-independent human prostate cancer LNCaP C-81 cells. Oncogene. 2003;22(5):781-96.
[16] Stumptner C, Heid H, Fuchsbichler A, Hauser H, Mischinger HJ, Zatloukal K, Denk H. Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent. Am J Pathol. 1999;154(6):1701-10.
[17] Waghray A, Keppler D, Sloane BF, Schuger L, Chen YQ. Analysis of a truncated form of cathepsin H in human prostate tumor cells. J Biol Chem. 2002;277(13):11533-8.
[18] Tan ST, Velickovic M, Ruger BM, Davis PF. Cellular and extracellular markers of hemangioma. Plast Reconstr Surg. 2000;106(3):529-38.
[19] Koroleva EP, Lagarkova MA, Mesheryakov AA, Scanlan MJ, Old LJ, Nedospasov SA, Kuprash DV. Serological identification of antigens associated with renal cell carcinoma. Russ J Immunol. 2002;7(3):229-38.
[20] Uemura M, Nouso K, Kobayashi Y, Tanaka H, Nakamura S, Higashi T, Ono T, Nakayama E, Hanafusa T, Shiratori Y. Identification of the antigens predominantly reacted with serum from patients with hepatocellular carcinoma. Cancer. 2003;97(10):2474-9.
[21] Moncrieff CL, Bailey ME, Morrison N, Johnson KJ. Cloning and chromosomal localization of human Cdc42-binding protein kinase beta. Genomics. 1999;57(2):297-300.
[22] Kaneko K, Satoh K, Masamune A, Satoh A, Shimosegawa T. Myosin light chain kinase inhibitors can block invasion and adhesion of human pancreatic cancer cell lines. Pancreas. 2002;24(1):34-41.
[23] Rae FK, Hooper JD, Nicol DL, Clements JA. Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors. Mol Carcinog. 2001;32(1):44-53.