HMMC ‐1, a human monoclonal antibody to fucosylated core 1 O‐glycan, suppresses growth of uterine endometrial cancer cells

HMMC ‐1 is a human monoclonal antibody that reacts with a fucosylated and extended core 1 O‐glycan, Fucα1‐2Galβ1‐4GlcNAcβ1‐3Galβ1‐3GalNAc‐Ser/Thr, as an epitope. In the present study, we examined the effects of HMMC ‐1 on cell proliferation of two human uterine endometrial cancer cell lines, HEC 8 and HEC 9, to investigate the role of glycoproteins bearing the HMMC ‐1 epitope in cancer progression. HEC 9 cells expressed high levels of the HMMC ‐1 epitope, but HMMC ‐1 reactivity was hardly detected in HEC 8 cells. In a mouse model of lymph node metastasis using orthotopic implantation, HEC 8 and HEC 9 showed low (10%) and high (80%) metastatic potency, respectively. Growth of HEC 9, but not HEC 8, was remarkably inhibited by addition of HMMC ‐1 to the culture medium. Cell cycle analysis and expression analysis showed that HMMC ‐1 treatment increased the G 1 phase population of HEC 9 cells and induced cyclin‐dependent kinase inhibitors p16 and p21. Two glycoproteins, 97 and 137 k D a, with a strong reactivity to HMMC ‐1 were purified, and the 97‐k D a glycoprotein was identified as CD 166, an immunoglobulin superfamily cell adhesion molecule assumed to be involved in cancer metastasis. CD 166 gene‐silencing dramatically reduced HMMC ‐1 epitope expression and growth in HEC 9 cells, indicating that CD 166 is the primary glycoprotein presenting the HMMC ‐1 epitope in HEC 9 cells. Collectively, HMMC ‐1 might arrest the cell cycle in the G 1 phase by binding to O‐glycans on the CD 166 expressed in HEC 9 cells, raising the possibility that HMMC ‐1 extensively inhibits invasive growth of HMMC ‐1 epitope‐positive uterine endometrial cancer cells by targeting the cancer‐associated form of CD 166. ( Cancer Sci 2013; 104: 62–69)