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Integrated glycomic analysis of ovarian cancer side population cells.

ABSTRACT: 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, ?2,3-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.

SUBMITTER: Zhao R

PROVIDER: S-EPMC5103398 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Integrated glycomic analysis of ovarian cancer side population cells.

Zhao Ran R Liu Xiaoxia X Wang Yisheng Y Jie Xiaoxiang X Qin Ruihuan R Qin Wenjun W Zhang Mengyu M Tai Haiyan H Yang Caiting C Li Lili L Peng Peike P Shao Miaomiao M Zhang Xingwang X Wu Hao H Ruan Yuanyuan Y Xu Congjian C Ren Shifang S Gu Jianxin J

Clinical proteomics 20161110

<h4>Background</h4>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 ultim ...[more]

PMID: 27833472

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Project description:The side population (SP), recently identified in several normal tissues and in a variety of tumors, may comprise cells endowed with stem cell features. In this study, we investigated the presence of SP in epithelial ovarian cancer (EOC) and found it in 4 out of 6 primary cultures from xenotransplants, as well as in 9 out of 25 clinical samples analyzed. SP cells from one xenograft bearing a large SP fraction were characterized in detail and they were capable of recreate the full repertoire of cancer cell populations observed in the parent tumor. Moreover, SP cells had higher proliferation rates, were much less apoptotic compared to non-SP cells, and generated tumors more rapidly than non-SP cells. We also investigated the effects of interferon-alfa (IFN-alpha), a cytokine which has been widely used to treat solid tumors, on EOC cells and observed that IFN-alpha exerts marked anti-proliferative and pro-apoptotic effects on primary cultures containing SP cells. IFN-alfa-treatment invariably caused a dramatic reduction in SP size in tumor cell lines of different origin and in normal bone-marrow SP cells, associated with a distinctive transcriptional profile. Gene therapy with human IFN-alpha resulted in regression of established tumors bearing a large SP fraction, which was not observed when tumors bearing low SP levels were treated. These findings could have relevant clinical implications since they imply that tumors bearing large SP numbers - albeit rare - could be sensitive to IFN-alpha treatment. Experiment Overall Design: 4 Affymetrix microarrays: Experiment Overall Design: 2 technical replicates: Ovarian cancer, untreated Side Population, rep1 Experiment Overall Design: Ovarian cancer, untreated Side Population, rep2 Experiment Overall Design: + Experiment Overall Design: 2 technical replicates: Ovarian cancer, IFN-alpha treated Side Population, rep1 Experiment Overall Design: Ovarian cancer, IFN-alpha treated Side Population, rep2

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Integrated glycomic analysis of ovarian cancer side population cells.

Publications

Integrated glycomic analysis of ovarian cancer side population cells.

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