Localization and characterization of melanoma-associated glycosaminoglycans: differential expression of chondroitin and heparan sulfate epitopes in melanoma.
Glycosaminoglycans (GAGs) are anionic polysaccharides present on cells and in the extracellular matrix (ECM). They likely play a role in tumor formation because of their capacity to bind and modulate a variety of proteins including growth factors, cytokines, and proteases. Using a panel of (human) phage display-derived anti-GAG antibodies, the location and expression of GAG epitopes in human cutaneous melanocytic lesions was studied. Antibodies EW4E1 and EW4G2 identified a melanoma-associated chondroitin sulfate/heparan sulfate epitope, whereas antibody EW4B7 recognized a melanoma-associated heparan sulfate epitope. These antibodies showed a high reactivity with blood vessels and ECM in cutaneous melanoma tumors, whereas their reactivity with nevi was very low. Using a set of defined oligosaccharides it was established that sulfate groups are of main importance in the binding to the antibodies and that glycomimetics can mimic natural oligosaccharides. In xenografts of melanoma cell line MeL57, a strong association of GAG epitopes with an injected fluorescent fluid flow tracer was observed. In uveal melanoma antibody, EW4E1 proved to be a sensitive probe for the detection of the geometry of ECM structures, known to have prognostic value. Taken together, data indicate that in melanoma a defined set and location of GAG epitopes are present with possible functional significance.
Smetsers
Toon F C M
TF
Departments of Biochemistry, University Medical Centre Nijmegen, Nijmegen Centre for Molecular Life Sciences (NCMLS), 6500 HB Nijmegen, the Netherlands.
van de Westerlo
Els M A
EM
ten Dam
Gerdy B
GB
Clarijs
Ruud
R
Versteeg
Elly M M
EM
van Geloof
Winnie L
WL
Veerkamp
Jacques H
JH
van Muijen
Goos N P
GN
van Kuppevelt
Toin H
TH
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002807:Chondroitin / Q000096:biosynthesis / Q000276:immunology*; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D008545:Melanoma / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism; D019151:Peptide Library; D051381:Rats; D017208:Rats, Wistar; D012878:Skin Neoplasms / Q000098:blood supply / Q000276:immunology / Q000378:metabolism; D014183:Transplantation, Heterologous; D014604:Uveal Neoplasms / Q000098:blood supply / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D002807:Chondroitin; D000939:Epitopes; D006497:Heparan Sulfate; D009844:Oligosaccharides; D019151:Peptide Library