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Low O-acetylation of sialyl-Le(x) contributes to its overexpression in colon carcinoma metastases

Item Type:Article
Title:Low O-acetylation of sialyl-Le(x) contributes to its overexpression in colon carcinoma metastases
Creators Name:Mann, B. and Klussmann, E. and Vandamme-Feldhaus, V. and Iwersen, M. and Hanski, M.L. and Riecken, E.O. and Buhr, H.J. and Schauer, R. and Kim, Y.S. and Hanski, C.
Abstract:Two factors potentially determining the consistent overexpression of sialyl-Le(x) antigen in colon carcinoma and metastases were investigated: (i) the expression of the mucins MUC1 and MUC2, known to carry sialyl-Le(x), by Northern blotting; (ii) the extent of sialic acid O-acetylation, by Western blotting and HPLC. RNA and sialyl-Le(x)-positive mucins were purified from normal colonic mucosa (N), primary carcinomas (T) and their liver metastases (M). Northern blots showed that mRNA expression both of MUC1 and of MUC2 decreases during the progression of the disease, and is lowest in metastatic tissue. The expression of mucin-bound sialyl-Le(x) increased strongly from N to T and, to a lesser extent, to M. After alkali treatment of the mucins these differences disappeared, indicating that the total amount of mucin-bound sialyl-Le(x) is the same in the 3 types of tissues. The O-acetylation of mucin-bound sialyl-Le(x) gradually decreased from N to M. HPLC analysis showed that in N about 70%, in T 45% and in M only 20% of mucin-bound sialic acids are O-acetylated. Thus, the increase of sialyl-Le(x) detectable during colon-carcinoma progression is due to diminished O-acetylation and not to increased expression of mucin protein cores. The decrease of O-acetylation is therefore the primary chemical alteration contributing to colon carcinoma-associated overexpression of sialyl-Le(x).
Keywords:Acetylation, Carcinoma, Colorectal Neoplasms, Liver Neoplasms, Mucin-1, Mucin-2, Mucins, Oligosaccharides, Messenger RNA
Source:International Journal of Cancer
Page Range:258-264
Date:17 July 1997
Official Publication:https://doi.org/10.1002/(SICI)1097-0215(19970717)72:2<258::AID-IJC10>3.0.CO;2-C
PubMed:View item in PubMed

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