engleski

Glycophenotype of breast cancer stem cells treated with glucosylceramide synthase and phospholipase C - γ2 inhibitors.

Metastasis, tumor relapse and resistance to therapy remain the principal causes of death for breast cancer patients. The emerging paradigm posits that tumor progression is driven by a small subpopulation of cancer cancer stem cells that exhibit the ability to self-renew and the ability to regenerate the phenotypic heterogeneity of the parental tumor. Many cancer cellular functions have been discovered to be regulated by phospholipase C-gamma 2 (PLC) activation, suggesting that it represents an important therapeutic target for development of anticancer drugs. Here, we investigate the influence of a newly developed, small molecule PLC gamma inhibitor, with or without glucosylceramide synthase inhibitor (D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, D-PDMP) therapy, on the growth, survival and glycophenotype (CD15s and GM3) of breast cancer stem cells (CSCs: CD44+CD24-). MDA-MB-231 breast cancer cells were incubated with glucosylceramide synthase inhibitor (D-PDMP) and/or PLC gamma inhibitor. The viable cells were determined by the MTT assay. Flow cytometric analysis of cells positive to anti-CD44 and glycoantigens, and negative to CD24 was performed 48h after inhibitor treatment. Treatment of the MDA-MB-231 cells with the PLC gamma inhibitor decreased the number of total viable cells. Additional decrease was achieved after combined inhibitor treatment. Percentage of CSCs was significantly decreased only after PLC inhibitor alone treatment. CSC GM3 geometric mean fluorescence intensity (GMI) was increased after PLC inhibitor alone and combined inhibitor treatment. CSC CD15s GMI was slightly decreased after PLC inhibitor alone treatment but significantly after combined inhibitor treatment. PLC gamma inhibitor alone was the most effective against CSCs, but observed decrease of CSC CD15s GMI after combined inhibitor treatment indicates possible lower metastatic ability of dually treated cells.

breast; cancer stem cells; GM3; CD15s

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