Altered glycosylation of glycodelin in endometrial carcinoma

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http://hdl.handle.net/10138/318950

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Hautala , L C , Pang , P-C , Antonopoulos , A , Pasanen , A , Lee , C-L , Chiu , P C N , Yeung , W S B , Loukovaara , M , Bützow , R , Haslam , S M , Dell , A & Koistinen , H 2020 , ' Altered glycosylation of glycodelin in endometrial carcinoma ' , Laboratory Investigation , vol. 100 , no. 7 , pp. 1014-1025 . https://doi.org/10.1038/s41374-020-0411-x

Title: Altered glycosylation of glycodelin in endometrial carcinoma
Author: Hautala, Laura C.; Pang, Poh-Choo; Antonopoulos, Aristotelis; Pasanen, Annukka; Lee, Cheuk-Lun; Chiu, Philip C. N.; Yeung, William S. B.; Loukovaara, Mikko; Bützow, Ralf; Haslam, Stuart M.; Dell, Anne; Koistinen, Hannu
Contributor: University of Helsinki, Sanna Lehtonen research group
University of Helsinki, HUSLAB
University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, HUSLAB
University of Helsinki, Department of Clinical Chemistry and Hematology
Date: 2020-07
Language: eng
Number of pages: 12
Belongs to series: Laboratory Investigation
ISSN: 0023-6837
URI: http://hdl.handle.net/10138/318950
Abstract: Glycodelin 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 (Gal beta 1-4GlcNAc) 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. Glycodelin is a major endometrial glycoprotein. The authors analyzed glycan structures of endometrial carcinoma associated glycodelin and established a novel glycodelin-glycoform specific histochemical staining method. With this, they showed that glycodelin is differentially glycosylated in endometrial carcinoma tissue, as compared to normal endometrium, representing a neoantigen with potential clinical applications.
Subject: BREAST-CANCER
IN-SITU
MONOCLONAL-ANTIBODIES
PLACENTAL PROTEIN-14
CELL
BINDING
ADENOCARCINOMA
EXPRESSION
LECTINS
OLIGOSACCHARIDES
3111 Biomedicine
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