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

Molecules. 2021 Oct 1;26(19):5962. doi: 10.3390/molecules26195962.

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.

Keywords: mucins; neuraminidase; ovarian neoplasms; peritoneal dissemination; sialic acid.

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Epitopes / metabolism
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mucin-1 / genetics
  • Mucin-1 / immunology
  • Mucin-1 / metabolism*
  • N-Acetylneuraminic Acid / metabolism*
  • Neuraminidase / metabolism
  • Neuraminidase / pharmacology
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Peritoneal Neoplasms / pathology
  • Peritoneal Neoplasms / secondary
  • Peritoneum / cytology
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Epitopes
  • MUC1 protein, human
  • Mucin-1
  • Polysaccharides
  • Neuraminidase
  • N-Acetylneuraminic Acid