Department of Chemistry and Biochemistry , Texas Tech University , Lubbock , Texas 79409-1061 , United States.
J Proteome Res. 2019 Oct 4;18(10):3731-3740. doi: 10.1021/acs.jproteome.9b00429. Epub 2019 Sep 16.
Breast cancer is a leading cancer in women and is considered to be the second-most common metastatic cancer following lung cancer. An estimated 10-16% of breast cancer patients are suffering from brain metastasis, and the diagnostic cases of breast cancer brain metastasis are increasing. Nevertheless, the mechanisms behind this process are still unclear. Aberrant glycosylation has been proved to be related to many diseases and cancer metastasis. However, studies of N-glycan isomer function in breast cancer brain metastasis are limited. In this study, the expressions of N-glycan isomers derived from five breast cancer cell lines and one brain cancer cell line were investigated and compared to a brain-seeking cell line, 231BR, to acquire a better understanding of the role glycan isomers play in breast cancer brain metastasis. The high temperature nanoPGC-LC-MS/MS achieved an efficient isomeric separation and permitted the identification and quantitation of 144 isomers from 50 N-glycan compositions. There were significant expression alterations of these glycan isomers among the different breast cancer cell lines. The increase of total glycan abundance and sialylation level were observed to be associated with breast cancer invasion. With regard to individual isomers, the greatest number of sialylated isomers was observed along with significant expression alterations in 231BR, suggesting a relationship between glycan sialylation and breast cancer brain metastasis. Furthermore, the increase of the α2,6-sialylation level in 231BR likely contributes to the passage of breast cancer cells through the blood-brain barrier, thus facilitating breast cancer brain metastasis. Meanwhile, the upregulation of highly sialylated glycan isomers with α2,6-linked sialic acids were found to be associated with breast cancer metastasis. This investigation of glycan isomer expressions, especially the unique isomeric expression in brain-seeking cell line 231BR, provides new information toward understanding the potential roles glycan isomers play during breast cancer metastasis and more clues for a deeper insight of this bioprocess.
乳腺癌是女性中最常见的癌症之一，被认为是仅次于肺癌的第二大常见转移性癌症。据估计，10-16%的乳腺癌患者患有脑转移，乳腺癌脑转移的诊断病例正在增加。然而，这一过程背后的机制仍不清楚。异常糖基化已被证明与许多疾病和癌症转移有关。然而，关于 N-糖基异构体在乳腺癌脑转移中的作用的研究还很有限。在这项研究中，研究了来自五种乳腺癌细胞系和一种脑癌细胞系的 N-糖基异构体的表达，并与脑趋向性细胞系 231BR 进行了比较，以更好地了解糖基异构体在乳腺癌脑转移中的作用。高温纳米 PGCLC-MS/MS 实现了有效的异构体分离，并允许从 50 种 N-糖基组成中鉴定和定量 144 种异构体。在不同的乳腺癌细胞系中，这些糖基异构体的表达有显著的改变。总糖含量的增加和唾液酸化水平的升高与乳腺癌的侵袭有关。就个别异构体而言，在 231BR 中观察到最多的唾液酸化异构体，并且表达明显改变，这表明糖基唾液酸化与乳腺癌脑转移之间存在关系。此外，231BR 中α2,6-唾液酸化水平的增加可能有助于乳腺癌细胞通过血脑屏障，从而促进乳腺癌脑转移。同时，上调具有α2,6 连接唾液酸的高度唾液酸化糖基异构体与乳腺癌转移有关。对糖基异构体表达的研究，特别是对脑趋向性细胞系 231BR 中独特异构体表达的研究，为理解糖基异构体在乳腺癌转移过程中可能发挥的作用提供了新的信息，并为更深入地了解这一生物过程提供了更多线索。
