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Revealing the Biological Attributes of N‑Glycan Isomers in Breast Cancer Brain Metastasis Using Porous Graphitic Carbon (PGC) Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
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posted on 2019-09-16, 12:36 authored by Wenjing Peng, Mona Goli, Parvin Mirzaei, Yehia MechrefBreast 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.
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breast cancer brain metastasisrole glycan isomers231 BR50 N-glycan compositionsexpression alterationsBreast Cancer Brain MetastasisLiquid Chromatography-Tandem Mass Spectrometrybreast cancer cellssialylated glycan isomersN-glycan isomer functionglycan isomer expressionsbreast cancer cell linesPorous Graphitic Carbonbreast cancer invasionbrain-seeking cell linebrain cancer cell linebreast cancer patientsLC-MSPGCbrain-seeking cell line 231 BRbreast cancer metastasisroles glycan isomers
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