ALTERATIONS OF O-GLYCAN BIOSYNTHESIS IN HUMAN COLON-CANCER TISSUES
ALTERATIONS OF O-GLYCAN BIOSYNTHESIS IN HUMAN COLON-CANCER TISSUES
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DOI：
10.1093/glycob/4.6.873
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发表时间：
1994-12-01
期刊：
影响因子：
4.3
通讯作者：
BROCKHAUSEN, I
中科院分区：
文献类型：
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作者：
YANG, JM;BYRD, JC;BROCKHAUSEN, I
人类结肠癌与粘蛋白型碳水化合物链（O-聚糖）的抗原性和结构变化相关。为了阐明结肠癌中这些O-聚糖的生物合成的控制，我们研究了参与细长O-聚糖结构组装的糖基转移酶和磺基转移酶活性。我们分析了从20名患者的癌组织、邻近正常组织和远端正常组织制备的匀浆。几种转移酶活性在癌组织中显示出明显的变化。这些变化与先前发现的癌粘蛋白中O-聚糖丢失相关，但并不总是与匀浆中Tn、唾液酸TTn、T和Le（x）抗原的水平或与癌组织的分化状态和杜克分期或患者的血型、性别和年龄相关。UDP-GlcNAc：Gal NAc-R β 3-N-乙酰葡糖胺转移酶（其中GlcNAc是N-乙酰基-D-葡糖胺，GalNAc是N-乙酰基-D-半乳糖胺）合成O-聚糖核心3，GlcNAc β 1-3GalNAc-，CMP-唾液酸：GalNAc-肽α 6-唾液酸转移酶合成唾液酸-Tn抗原和对O-聚糖核心1，Gal β 1-3GalNAc-的磺基转移酶活性在癌症中被发现降低，UDP-GlcNAc：在癌症中，Gal β 1-3GalNAc β 6-N-乙酰葡糖胺基转移酶也降低，同时丧失合成I抗原和核心4，GlcNAc β 1-6（GlcNAc β 1-3）GalNAc-的能力。CMP-唾液酸：Gal β 1-3GalNAc-R α 3-唾液酸转移酶和GDP-岩藻糖：Gal β-R α 2-岩藻糖基转移酶，合成血型H决定簇，在癌症中与正常组织相比分别增加4倍和3至8倍。数据表明，结肠癌中抗原和粘蛋白结合的O-聚糖结构的生物合成受到复杂的控制机制的影响。
Human colon cancer is associated with antigenic and structural changes in mucin-type carbohydrate chains (O-glycans). To elucidate the control of the biosynthesis of these O-glycans in colon cancer, we have studied glycosyltransferase and sulphotransferase activities involved in the assembly of elongated O-glycan structures, We analysed homogenates prepared from cancer tissue, adjacent normal and distal normal tissue from 20 patients. Several transferase activities showed pronounced changes in cancer tissue. The changes correlate with previous findings of a loss of O-glycans in cancer mucins, but did not always correlate with levels of Tn, sialyl-TTn, T and Le(x) antigens in homogenates or with the differentiation status and Duke's stages of the cancer tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R beta 3-N-acetylglucosaminyltransferase (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetyl-D-galactosamine) synthesizing O-glycan core 3, GlcNAc beta 1-3GalNAc-, CMP-sialic acid: GalNAc-peptide alpha 6-sialyltransferase synthesizing the sialyl-Tn antigen and sulphotransferase activities towards O-glycan core 1, Gal beta 1-3GalNAc-, were found to be decreased in cancer, UDP-GlcNAc: Gal beta 1-3GalNAc beta 6-N-acetylglucosaminyltransferase was also decreased in cancer concomitant with a loss of the ability to synthesize the I antigen and core 4, GlcNAc beta 1-6(GlcNAc beta 1-3) GalNAc-. CMP-sialic acid: Gal beta 1-3GalNAc-R alpha 3-sialyltransferase and GDP-fucose: Gal beta-R alpha 2-fucosyltransferase, synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold increased, respectively, in cancer compared to normal tissue, The data suggest that the biosynthesis of antigens and mucin-bound O-glycan structures in colon cancer is subject to complex control mechanisms.