Document Detail

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