MtDNA depletion influences the transition of CD44 subtypes in human prostate cancer DU145 cells.
Our earlier study revealed that long-term ethidium bromide application causes mitochondrial DNA depletion in human prostate cancer DU145 cell line (DU145MtDP), and this DU145MtDP subline appears to have expanded CD44Bright cell population than its parental wild type DU145 cells (DU145WT). Increasing evidence suggests that CD44Bright cells are highly cancer stem cell like, but it is not clear about their dynamic transition between CD44Dim and CD44Bright phenotypes in prostate cancer cells, and how it is affected by mitochondrial DNA depletion. To address these questions, four cell subpopulations were isolated from both DU145WT and DU145MtDP cell lines based on their CD44 expression level and mitochondrial membrane potential. The cell motility and colony formation capability of the fluorescence activated cell sorting-sorted cell subpopulations were further examined. It was discovered in the DU145WT cells that CD44Dim cells could transit into both CD44Dim and CD44Bright phenotypes and that CD44Bright cells were prone to sustain their CD44Bright phenotype as renewal. However, such transition principle was altered in the DU145MtDP cells, in which CD44Bright cells showed similar capability to sustain a CD44Bright phenotype, while the transition of CD44Dim cells to CD44Bright were suppressed. It is concluded that mitochondrial DNA depletion in the human prostate cancer DU145 cells influences their renewal and CD44 subphenotype transition. Such alterations may be the driving force for the enrichment of CD44Bright DU145 cells after the mitochondrial DNA depletion, although the molecular mechanisms remain unclear.
['Li|Xiaoran|X|', 'Grigalavicius|Mantas|M|', 'Li|Yaqing|Y|', 'Li|Xiaoli|X|', 'Zhong|Yali|Y|', 'Huang|Ruixia|R|', 'Yu|Dandan|D|', 'Berge|Viktor|V|', 'Goscinski|Mariusz Adam|MA|', 'Kvalheim|Gunnar|G|', 'Nesland|Jahn M|JM|', 'Suo|Zhenhe|Z|']
D045744:Cell Line, Tumor D019070:Cell Lineage D002465:Cell Movement D049109:Cell Proliferation D004272:DNA, Mitochondrial D004996:Ethidium D005434:Flow Cytometry D015972:Gene Expression Regulation, Neoplastic D006801:Humans D018960:Hyaluronan Receptors D008297:Male D014411:Neoplastic Stem Cells D011471:Prostatic Neoplasms
CD44 DU145 mitochondrial membrane potential fluorescence activated cell sorting phenotypic inter-conversion