Profound Diversity of the N-Glycome from Microdissected Regions of Colorectal Cancer, Stroma, and Normal Colon Mucosa
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Aberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures. To overcome these obstacles, we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous, stromal, and healthy mucosa cells. N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry, enabling the differentiation and structural characterization of isomeric species. In total, 116 N-glycans were identified that showed profound differences in expression among cancer, stroma, and normal mucosa. In comparison with healthy mucosa, the cancer cells showed an increase in α2-6 sialylation and monoantennary N-glycans, as well as a decrease in bisected N-glycans. Moreover, specific sialylated and (sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers. In comparison with cancer, the stroma showed lower levels of oligomannosidic and monoantennary N-glycans, LewisA/X epitopes, and sulfation, as well as increased expression of (core-)fucosylation and α2-3 sialylation. Our study reveals the distinct N-glycomic profiles of different cell types in CRC and control tissues, proving the necessity of their separate analysis for the discovery of cancer-associated glycans.
Originalsprog | Engelsk |
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Tidsskrift | Engineering |
Vol/bind | 26 |
Sider (fra-til) | 32-43 |
Antal sider | 12 |
ISSN | 2095-8099 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The work was supported by the China Scholarship Council. The authors thank Dr. Oleg A. Mayboroda and Dr. Marco R. Bladergroen for their assistance with statistics.
Publisher Copyright:
© 2022 THE AUTHORS
ID: 362337998