Abstract

BackgroundOvarian 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.MethodsSix 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.ResultsExpression 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.ConclusionsGlycan structures, such as Tn, T, sT antigens, and core fucosylation may serve as biomarkers of ovarian cancer stem cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-016-9131-z) contains supplementary material, which is available to authorized users.

Highlights

  • Ovarian cancer is the most lethal gynecological malignancy due to its frequent recurrence and drug resistance even after successful initial treatment

  • We examined the cell cycle of side population (SP) cells: nearly 97.5 % were arrested in the G0/G1 state (Fig. 1e), whereas only 66.17 % of unsorted HO8910 pm cells were in the G1 state

  • Our findings suggested that SP cells expressed increased core fucose, Tn, T and sT antigens

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Summary

Introduction

Ovarian cancer is the most lethal gynecological malignancy due to its frequent recurrence and drug resistance even after successful initial treatment. 80 % of patients are Accumulating scientific evidence suggests that tumors are driven by relatively rare and biologically distinct cancer-initiating cells, so-called cancer stem cells (CSCs), which are capable of self-renewal and further differentiation [6,7,8]. These cells are resistant to regular chemotherapy because they remain quiescent for a long time, proliferate slowly and excrete drugs [7, 8]. Detecting and eliminating CSCs would prohibit relapse and improve survival of ovarian cancer patients [9].

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