Overexpression of α2,3sialyl T-antigen in breast cancer determined by miniaturized glycosyltransferase assays and confirmed using tissue microarray immunohistochemical analysis.
Overexpression of α2,3sialyl T-antigen in breast cancer determined by miniaturized glycosyltransferase assays and confirmed using tissue microarray immunohistochemical analysis.
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DOI：
10.1007/s10719-014-9548-4
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发表时间：
2014-10
影响因子：
3
通讯作者：
Neelamegham, Sriram
中科院分区：
文献类型：
--
作者：
Patil, Shilpa A.;Bshara, Wiam;Morrison, Carl;Chandrasekaran, E. V.;Matta, Khushi L.;Neelamegham, Sriram
癌症期间的聚糖结构改变调节疾病进展并代表临床生物标志物。该研究确定了癌症期间糖基转移酶活性变化与异常细胞表面肿瘤相关碳水化合物结构（TACA）相关的程度。为此，使用小型化酶活性测定和带有末端LacNAc I型（Gal β1，3GlcNAc）、LacNAc II型（Galβ1，4GlcNAc）和粘蛋白核心1/III型（Gal β 1，3GalNAc）结构的合成糖缀合物，测量了正常和肿瘤组织中唾液酸转移酶（sialylT）、岩藻糖基转移酶（fucT）和半乳糖基转移酶（galT）活性的变化。这些数据与TACA使用包含115个乳腺癌和26个结肠癌标本的组织微阵列。结果表明，原发性人乳腺和结肠肿瘤，而不是邻近的正常组织，表达升高的β 1，3 galT和α2，3 sialylT活性，其可以形成α2，3唾液酸化III型聚糖（Siaα2，3Galβ1，3GalNAc）。前列腺肿瘤没有表现出这种升高的酶活性。α 1，3/4fucT活性在乳腺组织中较高，但在结肠组织中不较高。利用组织切片和组织微阵列的组织化学分析验证了基于酶学的乳腺肿瘤中增强的α2，3唾液酸化III型结构的预测。在此，识别Galβ1，3GalNAc的两种标记物（花生凝集素和mAb A78-G/A7）的结合在乳腺肿瘤中升高，而正常对照中没有，仅在唾液酸酶处理后。这些抗原在结肠肿瘤中也上调，尽管程度较低。α2，3唾液酸化III型表达与患者HER 2表达和乳腺转移潜能呈负相关。总的来说，glycoT活性的酶学测量可预测癌症期间聚糖结构的变化。乳腺肿瘤中α2，3唾液酸化T抗原O-聚糖的高表达。从线性核心-1聚糖到其他表位的转化可能伴随转移。
Glycan structure alterations during cancer regulate disease progression and represent clinical biomarkers. The study determined the degree to which changes in glycosyl transferase activities during cancer can be related to aberrant cell-surface tumor associated carbohydrate structures (TACA). To this end, changes in sialyltransferase (sialylT), fucosyltransferase (fucT) and galactosyltransferase (galT) activity were measured in normal and tumor tissue using a miniaturized enzyme activity assay and synthetic glycoconjugates bearing terminal LacNAc Type-I (Galβ1,3GlcNAc), LacNAc Type-II (Galβ1,4GlcNAc), and mucin core-1/Type-III (Galβ1,3GalNAc) structures. These data were related to TACA using tissue microarrays containing 115 breast and 26 colon cancer specimen. The results show that primary human breast and colon tumors, but not adjacent normal tissue, express elevated β1,3 galT and α2,3sialylT activity that can form α2,3sialylated Type-III glycans (Siaα2,3Galβ1,3GalNAc). Prostate tumors did not exhibit such elevated enzymatic activities. α1,3/4fucT activity was higher in breast, but not colon tissue. The enzymology based prediction of enhanced α2,3sialylated Type-III structures in breast tumors was verified using histochemical analysis of tissue sections and tissue microarrays. Here, the binding of two markers that recognize Galβ1,3GalNAc (peanut lectin and mAb A78-G/A7) was elevated in breast tumor, but not normal control, only upon sialidase treatment. These antigens were also upregulated in colon tumors though to a lesser extent. α2,3sialylated Type-III expression correlated inversely with patient HER2 expression and breast metastatic potential. Overall, enzymology measurements of glycoT activity predict glycan structure changes during cancer. High expression of the α2,3sialylated T-antigen O-glycans occur in breast tumors. A transformation from linear core-1 glycan to other epitopes may accompany metastasis.
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影响因子：
4.8
作者：
Marathe, Dhananjay D.;Chandrasekaran, E. V.;Neelamegham, Sriram
通讯作者：
Neelamegham, Sriram
DOI：
10.1016/j.biocel.2009.09.010
发表时间：
2010-01-01
影响因子：
4
作者：
Carvalho, A. S.;Harduin-Lepers, A.;Reis, C. A.
通讯作者：
Reis, C. A.
DOI：
10.1111/j.1432-1033.1995.607_2.x
发表时间：
1995-10-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BROCKHAUSEN, I;YANG, JM;TAYLORPAPADIMITRIOU, J
通讯作者：
TAYLORPAPADIMITRIOU, J
影响因子：
6.4
作者：
Park, Seung-Yeol;Lee, Sung-Hyeon;Kim, Jung Hoe
通讯作者：
Kim, Jung Hoe
影响因子：
4.8
作者：
M端ller, S;Hanisch, FG
通讯作者：
Hanisch, FG