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A Possible Inhibitory Role of Sialic Acid on MUC1 in Peritoneal Dissemination of Clear Cell-Type Ovarian Cancer Cells.

ABSTRACT: The role of sialic acids on MUC1 in peritoneal dissemination of ovarian cancer cells was investigated. A human ovarian carcinoma cell line, ES-2, was transfected with full-length MUC1 containing 22 or 42 tandem repeats. These transfectants were less adherent to monolayers of patient-derived mesothelial cells than ES-2/mock transfectants. When these cells were inoculated into the abdominal cavity of female nude mice, mice that had received the transfectants showed better survival. When the transfectants were mixed with sialidase and injected, the survival was poorer, whereas when they were mixed with N-acetyl-2,3-dehydro-2-deoxyneuraminic acid, a sialidase inhibitor, the survival was significantly prolonged. These behaviors, concerned with peritoneal implantation and dissemination observed in vitro and in vivo, were dependent on the expression of MUC1. Therefore, sialic acid linked to MUC1 in the form, at least in part, of sialyl-T, as shown to be recognized by monoclonal antibody MY.1E12, is responsible for the suppression of adhesion of these cells to mesothelial cells and the suppression of peritoneal implantation and dissemination.

SUBMITTER: Tamada Y

PROVIDER: S-EPMC8512441 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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A Possible Inhibitory Role of Sialic Acid on MUC1 in Peritoneal Dissemination of Clear Cell-Type Ovarian Cancer Cells.

Tamada Yutaka Y Nomura Hiroyuki H Aoki Daisuke D Irimura Tatsuro T

Molecules (Basel, Switzerland) 20211001 19

The role of sialic acids on MUC1 in peritoneal dissemination of ovarian cancer cells was investigated. A human ovarian carcinoma cell line, ES-2, was transfected with full-length MUC1 containing 22 or 42 tandem repeats. These transfectants were less adherent to monolayers of patient-derived mesothelial cells than ES-2/mock transfectants. When these cells were inoculated into the abdominal cavity of female nude mice, mice that had received the transfectants showed better survival. When the transf ...[more]

PMID: 34641504

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Project description:Epithelial ovarian cancer (EOC) is a rather rare but lethal disease that is usually diagnosed at an advanced stage; this is due to a lack of early diagnostic markers. At the time being, less than a quarter of patients are diagnosed when the tumor has not metastasized yet. In previous work, we demonstrated that antennarity, fucosylation, and sialylation increased in EOC patients and built a glycan-based score that was able to diagnose EOC better than CA125, the routine diagnostic marker, does. To date, little attention had been paid to the sialic acid linkages of N-glycans in the context of blood biomarker research. In this work, the sialic acid linkages of the serum glycome of ovarian cancer patients were investigated for the first time by MALDI-TOF-MS. To this end, we released N-glycans, derivatized sialic acids solely in a linkage-specific way and measured glycome profiles by MALDI-TOF mass spectrometry. A statistically significant decrease was observed between late stage patients and controls or early stage patients for high-mannose, hybrid-type, complex-type asialylated, bi, tri- and tetraantennary sialylated structures. A significant decrease of monosialylated monoantennary N-glycan structures was observed in early and late stage EOC when compared to healthy controls. Statistically significant increases were observed in early and late stage patients compared to controls for tri, tetraantennary fucosylated structures, afucosylated, and fucosylated triantennary structures taken as α-2,3-linked/α-2,6-linked sialic acid ratio. Moreover, all afucosylated and fucosylated structures taken as α-2,3-linked/α-2,6-linked sialic acid ratio and the α-2,3-linked/α-2,6-linked sialic acid ratio of all sialylated structures were increased significantly for early and late stage EOC patients when compared to healthy controls. Finally, ROC curves were built for the most significant glycan combinations and we were able to show that the serum glycome sialic acid ratio could enhance ovarian cancer diagnosis as sialic acid linkage modulations arise even in early stage ovarian cancer.

Dataset Information

A Possible Inhibitory Role of Sialic Acid on MUC1 in Peritoneal Dissemination of Clear Cell-Type Ovarian Cancer Cells.

Publications

A Possible Inhibitory Role of Sialic Acid on MUC1 in Peritoneal Dissemination of Clear Cell-Type Ovarian Cancer Cells.

Similar Datasets

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