| HMMC-1, a human monoclonal antibody to fucosylated core 1 O-glycan, suppresses growth of uterine endometrial cancer cells. | |
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MedLine Citation:
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PMID: 23035753 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 this 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 may 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. |
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Authors:
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Fumiko Oikawa; Kyoko Kojima-Aikawa; Fumika Inoue; Atsushi Suzuki; Kyoko Tanaka; Eiichiro Tominaga; Daisuke Aoki |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-5 |
Journal Detail:
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Title: Cancer science Volume: - ISSN: 1349-7006 ISO Abbreviation: Cancer Sci. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 Japanese Cancer Association. |
Affiliation:
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Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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