Published online before print August 23, 2007

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(American Journal of Pathology. 2007;171:1324-1333.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070111

Antibody GD3G7 Selected against Embryonic Glycosaminoglycans Defines Chondroitin Sulfate-E Domains Highly Up-Regulated in Ovarian Cancer and Involved in Vascular Endothelial Growth Factor Binding

Gerdy B. ten Dam^*, Els M.A. van de Westerlo^*, Anurag Purushothaman, Radu V. Stan, Johan Bulten, Fred C.G.J. Sweep^¶, Leon F. Massuger^||, Kazuyuki Sugahara and Toin H. van Kuppevelt^*

From the Department of Biochemistry,^* Nijmegen Center for Molecular Life Sciences, and the Departments of Pathology, Chemical Endocrinology,^¶ and Obstetrics and Gynaecology,|| Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; the Department of Biochemistry, Kobe Pharmaceutical University, Kobe, Japan; and the Department of Pathology, Dartmouth Medical School, Lebanon, New Hampshire

Chondroitin sulfate (CS) is abundantly present in the tumor stroma, and tumor-specific CS modifications might be potential targets to influence tumor development. We applied the phage display technology to select antibodies that identify these tumor-specific CS modifications. Antibody GD3G7 was selected against embryonic glycosaminoglycans, and it reacted strongly with CS-E (rich in GlcA-GalNAc4S6S units). In ovarian adenocarcinomas, strong expression of this CS-E epitope was found in the extracellular matrix, and occasionally on tumor cells. No expression was found in normal ovary and cystadenomas. Differential expression was found in ovarian carcinoma cell lines, which correlated with the gene expression of the GalNAc4S-6st enzyme, involved in biosynthesis of CS-E. Vascular endothelial growth factor (VEGF)-sensitive fenestrated (in normal tissues) and tumor blood vessels were both identified by antibody GD3G7, which might implicate a role for CS-E in VEGF biology. VEGF bound to CS-E and antibody GD3G7 could compete for binding of VEGF to CS-E. In conclusion, antibody GD3G7 identified rare CS-E-like structures that were strongly expressed in ovarian adenocarcinomas. This antibody might therefore be instrumental for identifying tumor-related CS alterations.

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