Dermatan sulfate domains defined by the novel antibody GD3A12, in normal tissues and ovarian adenocarcinomas.
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.
Department of Biochemistry 280, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen Medical Center, PO. Box 9101, 6500HB Nijmegen, The Netherlands. g.tendam@ncmls.ru.nl
Gerdy B
GB
Ten Dam
Shuhei
S
Yamada
Fumi
F
Kobayashi
Anurag
A
Purushothaman
Els M A
EM
van de Westerlo
Johan
J
Bulten
Anders
A
Malmström
Kazuyuki
K
Sugahara
Leon F
LF
Massuger
Toin H
TH
van Kuppevelt
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D045744:Cell Line, Tumor; D003871:Dermatan Sulfate / Q000276:immunology / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D000939:Epitopes; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D000939:Epitopes; D003871:Dermatan Sulfate