Glycosaminoglycans as novel target in antitumor therapy.
Considering the importance of intercellular contacts in the metastasis of malignant tumours drug action on glycosaminoglycan production as one of the underlying mechanisms in metastasis was investigated. 5-hexyl-2-deoxyuridine/HUdR/was shown to inhibit the conversion of glucosamine to UDP-sugars. Consequently various glycoconjugates were affected, especially the synthesis of heparan sulfate was reduced. It is noteworthy that HUdR inhibited the synthesis of glycosaminoglycans in tumour cells with high metastatic capacity. The biological consequence of the alterations in glycosaminoglycan production was studied on measuring HUdR action on cell surface markers, microinvasion and tumour metastasis in experimental systems. It was concluded that HUdR has remarkable antimetastatic activity which by all probability is due to the inhibition of heparane sulfate synthesis.
Jeney
A
A
I. Institute of Pathology and Experimental Cancer Research, Semmelweis Medical University, Budapest, Hungary.
Timár
J
J
Pogány
G
G
Paku
S
S
Moczár
E
E
Mareel
M
M
Otvös
L
L
Kopper
L
L
Lapis
K
K
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005354:Fibrosarcoma / Q000473:pathology; D005944:Glucosamine / Q000378:metabolism; D006001:Glycoconjugates / Q000378:metabolism; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D011990:Receptors, Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014539:Uridine Diphosphate Sugars / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D006001:Glycoconjugates; D006025:Glycosaminoglycans; D011990:Receptors, Transferrin; D014539:Uridine Diphosphate Sugars; C064952:5-hexyl-2'-deoxyuridine; D005944:Glucosamine; D003857:Deoxyuridine