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Article: Altered glycosylation of glycodelin in endometrial carcinoma

TitleAltered glycosylation of glycodelin in endometrial carcinoma
Authors
KeywordsDiagnostic markers
Endometrial cancer
Glycoconjugates
Immunohistochemistry
Mass spectrometry
Issue Date2020
PublisherSpringer for United States and Canadian Academy of Pathology (USCAP). The Journal's web site is located at http://www.nature.com/labinvest/
Citation
Laboratory Investigation, 2020, v. 100 n. 7, p. 1014-1025 How to Cite?
AbstractGlycodelin is a major glycoprotein expressed in reproductive tissues, like secretory and decidualized endometrium. It has several reproduction related functions that are dependent on specific glycosylation, but it has also been found to drive differentiation of endometrial carcinoma cells toward a less malignant phenotype. Here we aimed to elucidate whether the glycosylation and function of glycodelin is altered in endometrial carcinoma as compared with a normal endometrium. We carried out glycan structure analysis of glycodelin expressed in HEC-1B human endometrial carcinoma cells (HEC-1B Gd) by mass spectrometry glycomics strategies. Glycans of HEC-1B Gd were found to comprise a typical mixture of high-mannose, hybrid, and complex-type N-glycans, often containing undecorated LacNAc (Galβ1–4GlcNAc) antennae. However, several differences, as compared with previously reported glycan structures of normal human decidualized endometrium-derived glycodelin isoform, glycodelin-A (GdA), were also found. These included a lower level of sialylation and more abundant poly-LacNAc antennae, some of which are fucosylated. This allowed us to select lectins that showed different binding to these classes of glycodelin. Despite the differences in glycosylation between HEC-1B Gd and GdA, both showed similar inhibitory activity on trophoblast cell invasion and peripheral blood mononuclear cell proliferation. For the detection of cancer associated glycodelin, we established a novel in situ proximity-ligation based histochemical staining method using a specific glycodelin antibody and UEAI lectin. We found that the UEAI reactive glycodelin was abundant in endometrial carcinoma, but virtually absent in normal endometrial tissue even when glycodelin was strongly expressed. In conclusion, we established a histochemical staining method for the detection of endometrial carcinoma-associated glycodelin and showed that this specific glycodelin is exclusively expressed in cancer, not in normal endometrium. Similar methods can be used for studies of other glycoproteins.
Persistent Identifierhttp://hdl.handle.net/10722/284950
ISSN
2019 Impact Factor: 4.197
2015 SCImago Journal Rankings: 2.133
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorHautala, LC-
dc.contributor.authorPang, PC-
dc.contributor.authorAntonopoulos, A-
dc.contributor.authorPasanen, A-
dc.contributor.authorLee, CL-
dc.contributor.authorChiu, PCN-
dc.contributor.authorYeung, WSB-
dc.contributor.authorLoukovaara, Mikko-
dc.contributor.authorBützow, Ralf-
dc.contributor.authorHaslam, SM-
dc.contributor.authorDell, Anne-
dc.contributor.authorKoistinen, H-
dc.date.accessioned2020-08-07T09:04:45Z-
dc.date.available2020-08-07T09:04:45Z-
dc.date.issued2020-
dc.identifier.citationLaboratory Investigation, 2020, v. 100 n. 7, p. 1014-1025-
dc.identifier.issn0023-6837-
dc.identifier.urihttp://hdl.handle.net/10722/284950-
dc.description.abstractGlycodelin is a major glycoprotein expressed in reproductive tissues, like secretory and decidualized endometrium. It has several reproduction related functions that are dependent on specific glycosylation, but it has also been found to drive differentiation of endometrial carcinoma cells toward a less malignant phenotype. Here we aimed to elucidate whether the glycosylation and function of glycodelin is altered in endometrial carcinoma as compared with a normal endometrium. We carried out glycan structure analysis of glycodelin expressed in HEC-1B human endometrial carcinoma cells (HEC-1B Gd) by mass spectrometry glycomics strategies. Glycans of HEC-1B Gd were found to comprise a typical mixture of high-mannose, hybrid, and complex-type N-glycans, often containing undecorated LacNAc (Galβ1–4GlcNAc) antennae. However, several differences, as compared with previously reported glycan structures of normal human decidualized endometrium-derived glycodelin isoform, glycodelin-A (GdA), were also found. These included a lower level of sialylation and more abundant poly-LacNAc antennae, some of which are fucosylated. This allowed us to select lectins that showed different binding to these classes of glycodelin. Despite the differences in glycosylation between HEC-1B Gd and GdA, both showed similar inhibitory activity on trophoblast cell invasion and peripheral blood mononuclear cell proliferation. For the detection of cancer associated glycodelin, we established a novel in situ proximity-ligation based histochemical staining method using a specific glycodelin antibody and UEAI lectin. We found that the UEAI reactive glycodelin was abundant in endometrial carcinoma, but virtually absent in normal endometrial tissue even when glycodelin was strongly expressed. In conclusion, we established a histochemical staining method for the detection of endometrial carcinoma-associated glycodelin and showed that this specific glycodelin is exclusively expressed in cancer, not in normal endometrium. Similar methods can be used for studies of other glycoproteins.-
dc.languageeng-
dc.publisherSpringer for United States and Canadian Academy of Pathology (USCAP). The Journal's web site is located at http://www.nature.com/labinvest/-
dc.relation.ispartofLaboratory Investigation-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectDiagnostic markers-
dc.subjectEndometrial cancer-
dc.subjectGlycoconjugates-
dc.subjectImmunohistochemistry-
dc.subjectMass spectrometry-
dc.titleAltered glycosylation of glycodelin in endometrial carcinoma-
dc.typeArticle-
dc.identifier.emailLee, CL: kcllee@hku.hk-
dc.identifier.emailChiu, PCN: pchiucn@hku.hk-
dc.identifier.emailYeung, WSB: wsbyeung@hku.hk-
dc.identifier.authorityLee, CL=rp02515-
dc.identifier.authorityChiu, PCN=rp00424-
dc.identifier.authorityYeung, WSB=rp00331-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41374-020-0411-x-
dc.identifier.pmid32205858-
dc.identifier.pmcidPMC7312397-
dc.identifier.scopuseid_2-s2.0-85083377437-
dc.identifier.hkuros312374-
dc.identifier.volume100-
dc.identifier.issue7-
dc.identifier.spage1014-
dc.identifier.epage1025-
dc.publisher.placeUnited Kingdom-

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