title: HMMC-1, a human monoclonal antibody to fucosylated core 1 O-glycan, suppresses growth of uterine endometrial cancer cells.
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 G(1) 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 G(1) 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.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Oikawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kojima-Aikawa
authors.forename: Fumika
authors.initials: F
authors.lastname: Inoue
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Tominaga
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000276:immunology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000939:Epitopes; D005260:Female; D005326:Fetal Proteins / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011134:Polysaccharides / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000939:Epitopes; D005326:Fetal Proteins; D006023:Glycoproteins; D011134:Polysaccharides; D034741:RNA, Small Interfering; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C498094:HMMC-1 monoclonal antibody