Profound Diversity of the N-Glycome from Microdissected Regions of Colorectal Cancer, Stroma, and Normal Colon Mucosa
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Profound Diversity of the N-Glycome from Microdissected Regions of Colorectal Cancer, Stroma, and Normal Colon Mucosa. / Wang, Di; Madunić, Katarina; Zhang, Tao; Lageveen-Kammeijer, Guinevere S.M.; Wuhrer, Manfred.
I: Engineering, Bind 26, 2023, s. 32-43.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Profound Diversity of the N-Glycome from Microdissected Regions of Colorectal Cancer, Stroma, and Normal Colon Mucosa
AU - Wang, Di
AU - Madunić, Katarina
AU - Zhang, Tao
AU - Lageveen-Kammeijer, Guinevere S.M.
AU - Wuhrer, Manfred
N1 - Publisher Copyright: © 2022 THE AUTHORS
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Antibody response
KW - Colorectal cancer
KW - N-glycomics
KW - Porous graphitized carbon liquid chromatography mass spectrometry
KW - Tumor
U2 - 10.1016/j.eng.2022.08.016
DO - 10.1016/j.eng.2022.08.016
M3 - Journal article
AN - SCOPUS:85164625114
VL - 26
SP - 32
EP - 43
JO - Engineering
JF - Engineering
SN - 2095-8099
ER -
ID: 362337998