Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells.
Label-free in vivo molecular imaging of underglycosylated mucin-1 expression in tumour cells.
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DOI：
10.1038/ncomms7719
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发表时间：
2015-03-27
影响因子：
16.6
通讯作者：
Bulte, Jeff W. M.
中科院分区：
文献类型：
--
作者：
Song, Xiaolei;Airan, Raag D.;Arifin, Dian R.;Bar-Shir, Amnon;Kadayakkara, Deepak K.;Liu, Guanshu;Gilad, Assaf A.;van Zijl, Peter C. M.;McMahon, Michael T.;Bulte, Jeff W. M.
粘蛋白表达和糖基化的改变与癌症发展相关。低糖基化粘蛋白-1（uMUC 1）在大多数上皮来源的恶性腺癌（例如结肠癌、乳腺癌和卵巢癌）中过表达。其对应物MUC 1是富含含有多个可交换OH质子的聚糖的大聚合物，其易于通过化学交换饱和转移（CEST）MRI检测。我们在此显示MUC 1的去糖基化导致CEST信号减少>75%。与良性人类上皮细胞系MCF 10A和uMUC 1 −肿瘤细胞系U87相比，三种过表达uMUC 1的uMUC 1+人类恶性肿瘤细胞系（BT 20、HT 29和LS 174 T）显示出显著较低的CEST信号。此外，我们证明了体内CEST MRI能够区分植入小鼠脑中的LS 174 T和U87肿瘤细胞。这些结果表明，mucCEST MRI信号可用作无标记替代标记物，以非侵入性地评估粘蛋白糖基化和肿瘤恶性程度。 在大多数上皮起源的恶性腺癌中发现了糖基化不足的MUC 1（uMUC 1）的过度表达。在这里，作者使用化学交换饱和转移（CEST）MRI检测uMUC 1，并区分恶性和非恶性肿瘤。
Alterations in mucin expression and glycosylation are associated with cancer development. Underglycosylated mucin-1 (uMUC1) is overexpressed in most malignant adenocarcinomas of epithelial origin (for example, colon, breast and ovarian cancer). Its counterpart MUC1 is a large polymer rich in glycans containing multiple exchangeable OH protons, which is readily detectable by chemical exchange saturation transfer (CEST) MRI. We show here that deglycosylation of MUC1 results in >75% reduction in CEST signal. Three uMUC1+ human malignant cancer cell lines overexpressing uMUC1 (BT20, HT29 and LS174T) show a significantly lower CEST signal compared with the benign human epithelial cell line MCF10A and the uMUC1− tumour cell line U87. Furthermore, we demonstrate that in vivo CEST MRI is able to make a distinction between LS174T and U87 tumour cells implanted in the mouse brain. These results suggest that the mucCEST MRI signal can be used as a label-free surrogate marker to non-invasively assess mucin glycosylation and tumour malignancy. Overexpression of underglycosylated MUC1 (uMUC1) is found in most malignant adenocarcinomas of epithelial origin. Here the authors use chemical exchange saturation transfer (CEST) MRI to detect uMUC1 and to distinguish between malignant and nonmalignant tumours.
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影响因子：
3.8
作者：
Hanson, JM;Browell, DA;Pearson, JP
通讯作者：
Pearson, JP
影响因子：
6.4
作者：
Ghosh, Subrata K.;Uchida, Masashi;Medarova, Zdravka
通讯作者：
Medarova, Zdravka
影响因子：
78.5
作者：
Kufe, Donald W.
通讯作者：
Kufe, Donald W.
影响因子：
5.7
作者：
Jones, Craig K.;Huang, Alan;Xu, Jiadi;Edden, Richard A. E.;Schaer, Michael;Hua, Jun;Oskolkov, Nikita;Zaca, Domenico;Zhou, Jinyuan;McMahon, Michael T.;Pillai, Jay J.;van Zijl, Peter C. M.
通讯作者：
van Zijl, Peter C. M.
影响因子：
3.3
作者：
Chan, Kannie W. Y.;McMahon, Michael T.;Kato, Yoshinori;Liu, Guanshu;Bulte, Jeff W. M.;Bhujwalla, Zaver M.;Artemov, Dmitri;van Zijl, Peter C. M.
通讯作者：
van Zijl, Peter C. M.