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

Fumiko Oikawa, Kyoko Kojima-Aikawa, Fumika Inoue, Atsushi Suzuki, Kyoko Tanaka, Eiichirou Tominaga, Daisuke Aoki

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Abstract

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, HEC8 and HEC9, to investigate the role of glycoproteins bearing the HMMC-1 epitope in cancer progression. HEC9 cells expressed high levels of the HMMC-1 epitope, but HMMC-1 reactivity was hardly detected in HEC8 cells. In a mouse model of lymph node metastasis using orthotopic implantation, HEC8 and HEC9 showed low (10%) and high (80%) metastatic potency, respectively. Growth of HEC9, but not HEC8, 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 G1 phase population of HEC9 cells and induced cyclin-dependent kinase inhibitors p16 and p21. Two glycoproteins, 97 and 137 kDa, with a strong reactivity to HMMC-1 were purified, and the 97-kDa glycoprotein was identified as CD166, an immunoglobulin superfamily cell adhesion molecule assumed to be involved in cancer metastasis. CD166 gene-silencing dramatically reduced HMMC-1 epitope expression and growth in HEC9 cells, indicating that CD166 is the primary glycoprotein presenting the HMMC-1 epitope in HEC9 cells. Collectively, HMMC-1 might arrest the cell cycle in the G1 phase by binding to O-glycans on the CD166 expressed in HEC9 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 CD166.

Original languageEnglish
Pages (from-to)62-69
Number of pages8
JournalCancer Science
Volume104
Issue number1
DOIs
Publication statusPublished - 2013 Jan

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Uterine Neoplasms
Endometrial Neoplasms
Polysaccharides
Monoclonal Antibodies
Epitopes
Growth
Glycoproteins
G1 Phase
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p21
Neoplasm Metastasis
Neoplasms
Cell Adhesion Molecules
Gene Silencing
Cell Cycle Checkpoints
Culture Media
Immunoglobulins
Cell Cycle
Lymph Nodes
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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HMMC-1, a human monoclonal antibody to fucosylated core 1 O-glycan, suppresses growth of uterine endometrial cancer cells. / Oikawa, Fumiko; Kojima-Aikawa, Kyoko; Inoue, Fumika; Suzuki, Atsushi; Tanaka, Kyoko; Tominaga, Eiichirou; Aoki, Daisuke.

In: Cancer Science, Vol. 104, No. 1, 01.2013, p. 62-69.

Research output: Contribution to journalArticle

Oikawa, Fumiko ; Kojima-Aikawa, Kyoko ; Inoue, Fumika ; Suzuki, Atsushi ; Tanaka, Kyoko ; Tominaga, Eiichirou ; Aoki, Daisuke. / HMMC-1, a human monoclonal antibody to fucosylated core 1 O-glycan, suppresses growth of uterine endometrial cancer cells. In: Cancer Science. 2013 ; Vol. 104, No. 1. pp. 62-69.
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T1 - HMMC-1, a human monoclonal antibody to fucosylated core 1 O-glycan, suppresses growth of uterine endometrial cancer cells

AU - Oikawa, Fumiko

AU - Kojima-Aikawa, Kyoko

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AU - Suzuki, Atsushi

AU - Tanaka, Kyoko

AU - Tominaga, Eiichirou

AU - Aoki, Daisuke

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AB - 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, HEC8 and HEC9, to investigate the role of glycoproteins bearing the HMMC-1 epitope in cancer progression. HEC9 cells expressed high levels of the HMMC-1 epitope, but HMMC-1 reactivity was hardly detected in HEC8 cells. In a mouse model of lymph node metastasis using orthotopic implantation, HEC8 and HEC9 showed low (10%) and high (80%) metastatic potency, respectively. Growth of HEC9, but not HEC8, 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 G1 phase population of HEC9 cells and induced cyclin-dependent kinase inhibitors p16 and p21. Two glycoproteins, 97 and 137 kDa, with a strong reactivity to HMMC-1 were purified, and the 97-kDa glycoprotein was identified as CD166, an immunoglobulin superfamily cell adhesion molecule assumed to be involved in cancer metastasis. CD166 gene-silencing dramatically reduced HMMC-1 epitope expression and growth in HEC9 cells, indicating that CD166 is the primary glycoprotein presenting the HMMC-1 epitope in HEC9 cells. Collectively, HMMC-1 might arrest the cell cycle in the G1 phase by binding to O-glycans on the CD166 expressed in HEC9 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 CD166.

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