Expression of mucin 1 possessing a 3'-sulfated core1 in recurrent and metastatic breast cancer

Int J Cancer. 2015 Oct 1;137(7):1652-60. doi: 10.1002/ijc.29520. Epub 2015 Apr 7.

Abstract

Breast cancer is the most frequent cancer threatening the lives of women between the ages of 30 and 64. The cancer antigen 15-3 assay (CA15-3) has been widely used for the detection of breast cancer recurrence; however, its sensitivity and specificity are inadequate. We previously found that the breast cancer cell line YMBS secretes mucin 1 possessing 3'-sulfated core1 (3Score1-MUC1) into the medium. Therefore, we here evaluated whether 3Score1-MUC1 is secreted into the blood streams of breast cancer patients, and whether it can serve as an improved breast cancer marker. We developed a lectin-sandwich immunoassay, called Gal4/MUC1, using a 3'-sulfated core1-specific galectin-4 and a MUC1 monoclonal antibody. Using the Gal4/MUC1 assay method, we found that 3Score1-MUC1 was profoundly expressed in the blood streams of patients with recurrent and/or metastatic breast cancer. The positive ratio of the Gal4/MUC1 assay was higher than that of the CA15-3 assay in both primary (n = 240) and relapsed (n = 43) patients, especially in the latter of which the positive ratio of Gal4/MUC1 was 86%. whereas that of CA15-3 was 47%. Furthermore, serum Gal4/MUC1 levels could more sensitively reflect the recurrence of primary breast cancer patients after surgery. Therefore, the Gal4/MUC1 assay should be an excellent alternative to the CA15-3 tumor marker for tracking the recurrence and metastasis of breast cancer.

Keywords: 3′-sulfated core1; MUC1; breast cancer; galectin-4; metastasis; tumor marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / chemistry
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / blood
  • Breast Neoplasms / blood
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carbohydrate Sequence
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Galectin 4 / chemistry
  • Humans
  • Middle Aged
  • Molecular Sequence Data
  • Mucin-1 / biosynthesis*
  • Mucin-1 / blood
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / pathology

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Galectin 4
  • MUC1 protein, human
  • Mucin-1