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Dermatan sulfate domains defined by the novel antibody GD3A12, in normal tissues and ovarian adenocarcinomas

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Abstract

Dermatan sulfate (DS) expression in normal tissue and ovarian cancer was investigated using the novel, phage display-derived antibody GD3A12 that was selected against embryonic glycosaminoglycans (GAGs). Antibody GD3A12 was especially reactive with DS rich in IdoA-GalNAc4S disaccharide units. IdoA residues are important for antibody recognition as DS polymers with low numbers of IdoA residues were less reactive, and expression of the DS epimerase in ovarian carcinoma cells was associated with expression of the GD3A12 epitope. Moreover, staining of antibody GD3A12 was abolished by chondroitinase-B lyase digestion. Expression of DS domains defined by antibody GD3A12 was confined to connective tissue of most organs examined and presented as a typical fibrillar-type of staining. Differential expression of the DS epitopes recognized by antibodies GD3A12 and LKN1 (4/2,4 di-O-sulfated DS) was best seen in thymus and spleen, indicating differential expression of various DS domains in these organs. In ovarian carcinomas strong DS expression was found in the stromal parts, and occasionally on tumor cells. Partial co-localization in ovarian carcinomas was observed with decorin, versican and type I collagen suggesting a uniform distribution of this specific DS epitope. This unique anti-DS antibody may be instrumental to investigate the function, expression, and localization of specific DS domains in health and disease.

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Acknowledgments

The authors like to thank Dr M. Pavao (Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil) for the 2,6 DS and 4/2,4 DS samples. This work was supported by the Dutch Cancer Society, grant numbers 2002-2762 and 2008-4058 (to Gerdy B. ten Dam). The Human Frontier Science Program (RGP62/2004 to Toin H. van Kuppevelt and RGP18/2005 to Kazuyuki Sugahara) and the New Energy and Industrial Technology Development Organization (NEDO) (to Kazuyuki Sugahara).

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Authors and Affiliations

  1. Department of Biochemistry 280, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, PO. Box 9101, 6500 HB, Nijmegen, The Netherlands

    Gerdy B. ten Dam, Els M.A. van de Westerlo & Toin H. van Kuppevelt

  2. Laboratory of Proteoglycan Signaling and Therapeutics, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University Graduate School of Life Science, Sapporo, Hokkaido, 001-0021, Japan

    Shuhei Yamada, Fumi Kobayashi & Kazuyuki Sugahara

  3. Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe, 658-8558, Japan

    Anurag Purushothaman & Kazuyuki Sugahara

  4. Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    Johan Bulten

  5. Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    Leon F. Massuger

  6. Department of Experimental Medical Science, Lund University, BMC D12, 221 84, Lund, Sweden

    Anders Malmström

Authors
  1. Gerdy B. ten Dam
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  2. Shuhei Yamada
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  3. Fumi Kobayashi
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  4. Anurag Purushothaman
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  5. Els M.A. van de Westerlo
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  6. Johan Bulten
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  7. Anders Malmström
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  8. Kazuyuki Sugahara
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  9. Leon F. Massuger
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  10. Toin H. van Kuppevelt
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Correspondence to Gerdy B. ten Dam.

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ten Dam, G.B., Yamada, S., Kobayashi, F. et al. Dermatan sulfate domains defined by the novel antibody GD3A12, in normal tissues and ovarian adenocarcinomas. Histochem Cell Biol 132, 117–127 (2009). https://doi.org/10.1007/s00418-009-0592-2

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  • DOI: https://doi.org/10.1007/s00418-009-0592-2

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