Skip to main content

Advertisement

Log in

Ectopic expression of N-acetylglucosamine 6-O-sulfotransferase 2 in chemotherapy-resistant ovarian adenocarcinomas

  • Original Papers
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Mucinous and clear cell adenocarcinomas are the major histological types of ovarian epithelial cancer and are associated with a poor prognosis due to their resistance to chemotherapy. A novel tumor marker specific for ovarian mucinous and clear cell adenocarcinomas would be helpful for overcoming these serious diseases. We showed previously by enzymological characterization and RT-PCR that colonic mucinous adenocarcinoma tissues ectopically express GlcNAc6ST-2, a member of the carbohydrate 6-O-sulfotransferase family (Seko, A. et al. (2002) Glycobiology 12, 379–388). Here, we prepared a GlcNAc6ST-2-specific polyclonal antibody for immunohistochemical analysis and found that GlcNAc6ST-2 is ectopically expressed by not only colonic mucinous adenocarcinomas but also ovarian mucinous, clear cell and papillary serous adenocarcinomas. In contrast, solid serous adenocarcinomas, endometrioid adenocarcinomas, and mucinous adenomas expressed GlcNAc6ST-2 much less frequently or not at all. RT-PCR analysis confirmed that GlcNAc6ST-2 transcripts are expressed in ovarian mucinous adenocarcinomas but not in mucinous adenomas. In addition, immunohistochemical analysis using sulfated glycan-specific monoclonal antibodies showed that ovarian adenocarcinoma cells express GlcNAc 6-O-sulfated glycans, including an L-selectin ligand and its related glycans. These results indicate that GlcNAc6ST-2 would be a novel tumor antigen that is specifically expressed in ovarian mucinous, clear cell and papillary serous adenocarcinomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

Gal:

galactose

GalNAc:

N-acetylgalactosamine

GlcNAc:

N-acetylglucosamine

HRP:

horseradish peroxidase

LacNAc:

N-acetyllactosamine

References

  1. Rubin, S.C., Wong, G.Y., Curtin, J.P., Barakat, R.R., Hakes, T.B., Hoskins, W.J.: Platinum-based chemotherapy of high-risk stage I epithelial ovarian cancer following comprehensive surgical staging. Obstet. Gynecol. 82, 143–47 (1993)

    PubMed  CAS  Google Scholar 

  2. Hogberg, T., Carstensen, J., Simonsen, E.: Treatment results and prognostic factors in a population-based study of epithelial ovarian cancer. Gynecol. Oncol. 48, 38–49 (1993)

    Article  PubMed  CAS  Google Scholar 

  3. Shih, IeM., Kurman, R.J.: Ovarian tumorigenesis: A proposed model based on morphological and molecular genetic analysis. Am. J. Pathol. 164, 1511–18 (2004)

    PubMed  CAS  Google Scholar 

  4. Omura, G.A., Brady, M.F., Homesley, H.D., Yordan, E., Major, F.J., Buchsbaum, H.J., Park, R.C.: Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. J. Clin. Oncol. 9, 1138–50 (1991)

    PubMed  CAS  Google Scholar 

  5. Jacobs, I.J., Skates, S., Davies, A.P., Woolas, R.P., Jeyerajah, A., Weidemann, P., Sibley, K., Oram, D.H.: Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study. BMJ 313, 1355–58 (1996)

    PubMed  CAS  Google Scholar 

  6. Jacobs, I.J., Skates, S.J., MacDonald, N., Menon, U., Rosenthal, A.N., Davies, A.P., Woolas, R., Jeyarajah, A.R., Sibley, K., Lowe, D.G., Oram, D.H.: Screening for ovarian cancer: a pilot randomised controlled trial. Lancet 353, 1207–10 (1999)

    Article  PubMed  CAS  Google Scholar 

  7. Bast, R.C. Jr., Xu, F.J., Yu, Y.H., Barnhill, S., Zhang, Z., Mills, G.B.: CA 125: The past and the future. Int. J. Biol. Markers 13, 179–87 (1998)

    PubMed  CAS  Google Scholar 

  8. Seko, A., Nagata, K., Yonezawa, S., Yamashita, K.: Ectopic expression of a GlcNAc 6-O-sulfotransferase, GlcNAc6ST-2, in colonic mucinous adenocarcinoma. Glycobiology 12, 379–88 (2002)

    Article  PubMed  CAS  Google Scholar 

  9. Fukuda, M., Hiraoka, N., Akama, T.O., Fukuda, M.N.: Carbohydrate-modifying sulfotransferases: structure, function, and pathophysiology. J. Biol. Chem. 276, 47747–50 (2001)

    PubMed  CAS  Google Scholar 

  10. Bistrup, A., Bhakta, S., Lee, J.K., Belov, Y.Y., Gunn, M.D., Zuo, F.R., Huang, C.C., Kannagi, R., Rosen, S.D., Hemmerich, S.: Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin. J. Cell Biol. 145, 899–910 (1999)

    Article  PubMed  CAS  Google Scholar 

  11. Hemmerich, S., Bistrup, A., Singer, M.S., van Zante, A., Lee, J.K., Tsay, D., Peters, M., Carminati, J.L., Brennan, T.J., Carver-Moore, K., Leviten M et al.: Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes. Immunity 15, 237–47 (2001)

    Article  PubMed  CAS  Google Scholar 

  12. Yeh, J.C., Hiraoka, N., Petryniak, B., Nakayama, J., Ellies, L.G., Rabuka, D., Hindsgaul, O., Marth, J.D., Lowe, J.B., Fukuda, M.: Novel sulfated lymphocyte homing receptors and their control by a Core1 extension beta 1,3-N-acetylglucosaminyltransferase. Cell 105, 957–69 (2001)

    Article  PubMed  CAS  Google Scholar 

  13. Mitsuoka, C., Sawada-Kasugai, M., Ando-Furui, K., Izawa, M., Nakanishi, H., Nakamura, S., Ishida, H., Kiso, M., Kannagi, R.: Identification of a major carbohydrate capping group of the L-selectin ligand on high endothelial venules in human lymph nodes as 6-sulfo sialyl Lewis X. J. Biol. Chem. 273, 11225–33 (1998)

    Article  PubMed  CAS  Google Scholar 

  14. Uchimura, K., Muramatsu, H., Kadomatsu, K., Fan, Q.W., Kurosawa, N., Mitsuoka, C., Kannagi, R., Habuchi, O., Muramatsu, T.: Molecular cloning and characterization of an N-acetylglucosamine-6-O-sulfotransferase. J. Biol. Chem. 273, 22577–83 (1998)

    Article  PubMed  CAS  Google Scholar 

  15. Seko, A., Sumiya, J., Yonezawa, S., Nagata, K., Yamashita, K.: Biochemical differences between two types of N-acetylglucosamine:-6sulfotransferases in human colonic adenocarcinomas and the adjacent normal mucosa: Specific expression of a GlcNac:-6sulfotransferase in mucinous adenocarcinoma. Glycobiology 10, 919–29 (2000)

    Article  PubMed  CAS  Google Scholar 

  16. Lee, J.K., Bhakta, S., Rosen, S.D., Hemmerich, S.: Cloning and characterization of a mammalian N-acetylglucosamine-6-sulfotransferase that is highly restricted to intestinal tissue, Biochem. Biophys. Res. Coomun. 263, 543–9 (1999)

    Article  CAS  Google Scholar 

  17. Uchimura, K., El-Fasakhany, F.M., Hori, M., Hemmerich, S., Blink, S.E., Kansas, G.S., Kanamori, A., Kumamoto, K., Kannagi, R., Muramatsu, T.: Specificities of N-acetylglucosamine-6-O-sulfotransferases in relation to L-selectin ligand synthesis and tumor-associated enzyme expression. J. Biol. Chem. 277, 3979–84 (2002)

    Article  PubMed  CAS  Google Scholar 

  18. Federici, M.F., Kudryashov, V., Saigo, P.E., Finstad, C.L., Lloyd, K.O.: Selection of carbohydrate antigens in human epithelial ovarian cancers as targets for immunotherapy: serous and mucinous tumors exhibit distinctive patterns of expression. Int. J. Cancer 81, 193–98 (1999)

    Article  PubMed  CAS  Google Scholar 

  19. Tamada, Y., Iida, S., Aoki, D., Nozawa, S., Irimura, T.: Carbohydrate epitopes and mucins expressed by 17 human ovarian carcinoma cell lines. Oncol. Res. 11, 233–41 (1999)

    PubMed  CAS  Google Scholar 

  20. Phillips, M.L., Nudelman, E., Gaeta, F.C., Perez, M., Singhal, A.K., Hakomori, S., Paulson, J.C.: ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science 250, 1130–32 (1990)

    PubMed  CAS  Google Scholar 

  21. Takada, A., Ohmori, K., Yoneda, T., Tsuyuoka, K., Hasegawa, A., Kiso, M., Kannagi, R.: Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium. Cancer Res. 53, 354–61 (1993)

    PubMed  CAS  Google Scholar 

  22. Martin-Satue, M., Marrugat, R., Cancelas, J.A., Blanco, J.: Enhanced expression of alpha(1,3)-fucosyltransferase genes correlates with E-selectin-mediated adhesion and metastatic potential of human lung adenocarcinoma cells. Cancer Res. 58, 1544–50 (1998)

    PubMed  CAS  Google Scholar 

  23. Weston, B.W., Hiller, K.M., Mayben, J.P., Manousos, G.A., Bendt, K.M., Liu, R., Cusack, J.C. Jr.: Expression of human alpha(1,3)fucosyltransferase antisense sequences inhibits selectin-mediated adhesion and liver metastasis of colon carcinoma cells. Cancer Res. 59, 2127–35 (1999)

    PubMed  CAS  Google Scholar 

  24. Ichikawa, Y., Nishida, M., Suzuki, H., Yoshida, S., Tsunoda, H., Kubo, T., Uchida, K., Miwa, M.: Mutation of K-ras protooncogene is associated with histological subtypes in human mucinous ovarian tumors. Cancer Res. 54, 33–35 (1994)

    PubMed  CAS  Google Scholar 

  25. Zhang, H., Evertsson, S., Sun, X.: Clinicopathological and genetic characteristics of mucinous carcinomas in the colorectum. Int. J. Oncol. 14, 1057–61 (1999)

    PubMed  CAS  Google Scholar 

  26. Schuijer, M., Berns, E.M.: TP53 and ovarian cancer. Hum. Mutat. 21, 285–91 (2003)

    Article  PubMed  CAS  Google Scholar 

  27. Inoue, M., Ton, S.M., Ogawa, H., Tanizawa, O.: Expression of Tn and sialyl-Tn antigens in tumor tissues of the ovary. Am. J. Clin. Pathol. 96, 711–16 (1991)

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katsuko Yamashita.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kanoh, A., Seko, A., Ideo, H. et al. Ectopic expression of N-acetylglucosamine 6-O-sulfotransferase 2 in chemotherapy-resistant ovarian adenocarcinomas. Glycoconj J 23, 453–460 (2006). https://doi.org/10.1007/s10719-006-6979-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-006-6979-6

Keywords

Navigation