Integrated glycomic analysis of ovarian cancer side population cells.
BACKGROUND
Ovarian cancer is the most lethal gynecological malignancy due to its frequent recurrence and drug resistance even after successful initial treatment. Accumulating scientific evidence indicates that subpopulations of cancer cells with stem cell-like properties, such as so-called side population (SP) cells, are primarily responsible for these recurrences. A better understanding of SP cells may provide new clues for detecting and targeting these cancer-initiating cells and ultimately help to eradicate cancer. Changes in glycosylation patterns are remarkable features of SP cells. Here, we isolated SP cells from ovarian cancer cell lines and analyzed their glycosylation patterns using multiple glycomic strategies.


METHODS
Six high-grade serous ovarian cancer cell lines were used for SP cell isolation. Among them, HO8910 pm, which contained the highest proportion of SP cells, was used for glycomic analysis of SP cells. Cell lysate of SP cells and main population cells was applied to lectin microarray and mass spectrometry for glycan profiling. Differently expressed glycan structures were further verified by lectin blot, flow cytometry, and real-time PCR analysis of their relevant enzymes.


RESULTS
Expression of core fucosylated N-glycan and tumor-associated Tn, T and sT antigens were increased in SP cells. By contrast, SP cells exhibited decreased hybrid glycan, α2,3-linked sialic glycan and multivalent sialyl-glycan.


CONCLUSIONS
Glycan structures, such as Tn, T, sT antigens, and core fucosylation may serve as biomarkers of ovarian cancer stem cells.
Institute of Biomedical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Ran
R
Zhao
Obstetrics and Gynecology Hospital of Fudan University, 419 Fang-Xie Road, Shanghai, 200011 People's Republic of China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200032 People's Republic of China.
Xiaoxia
X
Liu
Obstetrics and Gynecology Hospital of Fudan University, 419 Fang-Xie Road, Shanghai, 200011 People's Republic of China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200032 People's Republic of China.
Yisheng
Y
Wang
Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, 200032 People's Republic of China.
Xiaoxiang
X
Jie
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Ruihuan
R
Qin
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Wenjun
W
Qin
Obstetrics and Gynecology Hospital of Fudan University, 419 Fang-Xie Road, Shanghai, 200011 People's Republic of China.
Mengyu
M
Zhang
Obstetrics and Gynecology Hospital of Fudan University, 419 Fang-Xie Road, Shanghai, 200011 People's Republic of China.
Haiyan
H
Tai
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Caiting
C
Yang
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Lili
L
Li
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Peike
P
Peng
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Miaomiao
M
Shao
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Xingwang
X
Zhang
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Hao
H
Wu
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Yuanyuan
Y
Ruan
Institute of Biomedical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.|Obstetrics and Gynecology Hospital of Fudan University, 419 Fang-Xie Road, Shanghai, 200011 People's Republic of China.|Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, 200032 People's Republic of China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200032 People's Republic of China.
Congjian
C
Xu
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Shifang
S
Ren
Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yi-Xueyuan Road, Shanghai, 200032 People's Republic of China.
Jianxin
J
Gu
Biomarker; Glycomic; Ovarian cancer stem cells; T antigen; Tn antigen; sT antigen