Heparan sulfate undergoes specific structural changes during the progression from human colon adenoma to carcinoma in vitro.
We report a detailed analysis of heparan sulfate (HS) structure using a model of human colon carcinogenesis. Metabolically radiolabeled HS was isolated from adenoma and carcinoma cells. The chain length of HS was the same in both cell populations (Mr 20,000; 45-50 disaccharides), and the chains contained on average of two sulfated domains (S domains), identified by heparinase I scission. This enzyme produced fragments of approximate size 7 kDa, suggesting that the S domains were evenly spaced in the intact HS chain. The degree of polymer sulfation and the patterns of sulfation were strikingly different between the two HS species. When compared with adenoma HS, the iduronic acid 2-O-sulfate content of the carcinoma-derived material was reduced by 33%, and the overall level of N-sulfation was reduced by 20%. However, the level of 6-O-sulfation was increased by 24%, and this was almost entirely attributable to an enhanced level of N-sulfated glucosamine 6-O-sulfate, a species whose data implied was mainly located in the mixed sequences of alternating N-sulfated and N-acetylated disaccharides. The results indicate that in the transition to malignancy in human colon adenoma cells, the overall molecular organization of HS is preserved, but there are distinct modifications in both the S domains and their flanking mixed domains that may contribute to the aberrant behavior of the cancer cell.
Jayson
G C
GC
Cancer Research Campaign Department, Medical Oncology, University of Manchester and Christie Hospital National Health Service Trust, Withington, Manchester M20 4BX, United Kingdom.
Lyon
M
M
Paraskeva
C
C
Turnbull
J E
JE
Deakin
J A
JA
Gallagher
J T
JT
D000236:Adenoma / Q000737:chemistry / Q000473:pathology*; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003110:Colonic Neoplasms / Q000737:chemistry / Q000473:pathology*; D006497:Heparan Sulfate / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D015394:Molecular Structure; D008970:Molecular Weight; D009608:Nitrous Acid / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry; D014407:Tumor Cells, Cultured
D006497:Heparan Sulfate; D009608:Nitrous Acid; D009844:Oligosaccharides