Glycoprotein B7-H3 Overexpression and Aberrant Glycosylation in Oral Cancer and Immune Response
Date Issued
2015
Date
2015
Author(s)
Chen, Jung-Tsu
Abstract
Oral cancer is the eleventh most-common cancer worldwide and the fifth most prevalent cancer in Taiwan. Although the incidence has decreased over the last decade, outcomes of oral cancer remain difficult with only 5% improvement in overall survival in the last 20 years. The five-year survival rate of oral cancer is about 50% and complete recovery is almost not possible as recurrence is occurred. It is partly due to the lack of effective early diagnosis and increasing environmental exposure to cancer-causing agents. It has been proved that aberrant glycosylation is involved in cellular transformation. To identify new markers for oral cancer, we employed a glycosylation probe to investigate the function of sialylated glycoproteins differentially expressed on oral cancer cells and B7-H3 was found to be significant. B7-H3 is a membrane protein originally identified from immune cells. It is a costimulatory molecule related with the proliferation and IFN-gamma production in T cells. B7-H3 is also found in a variety of cancers and correlated with tumor progression. The purpose of this study is to explore the role of B7-H3 involved in oral cancer. B7-H3 was found to be overexpressed in oral squamous cell carcinoma (OSCC) specimens and correlated with larger tumor size (p=0.0001), advanced clinical stage (p=0.004) and low survival rate in OSCC patients (B7-H3 labeling score >= 55%). In addition, knockdown of B7-H3 suppressed tumor cell proliferation, and restoration of B7-H3 expression enhanced tumor growth. We also observed differences in the glycoforms of B7-H3 between cancer and normal cells; higher fucosylation, higher branching and terminal alpha-galacosylation of N-linked glycans were observed in the cancer cells but not in the normal cells. Moreover, B7-H3 derived from Ca9-22 oral cancer cells had better interaction with the lectin receptors DC-SIGN and Langerin than B7-H3 derived from normal cells. Overall, this study demonstrates that B7-H3 overexpression with characteristic aberrant glycosylation correlates with tumor growth and immune response.
Subjects
CD276
cell proliferation
glycan sequencing
terminal alpha-galactose
SDGs
Type
thesis
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