CD133 Is Associated with Increased Melanoma Cell Survival after Multikinase Inhibition

Journal of Oncology
Cynthia M Simbulan-RosenthalDean S Rosenthal

Abstract

FDA-approved kinase inhibitors are now used for melanoma, including combinations of the MEK inhibitor trametinib, and BRAF inhibitor dabrafenib for BRAFV600 mutations. NRAS-mutated cell lines are also sensitive to MEK inhibition in vitro, and NRAS-mutated tumors have also shown partial response to MEK inhibitors. However, melanoma still has high recurrence rates due to subpopulations, sometimes described as "melanoma initiating cells," resistant to treatment. Since CD133 is a putative cancer stem cell marker for different cancers, associated with decreased survival, we examined resistance of patient-derived CD133(+) and CD133(-) melanoma cells to MAPK inhibitors. Human melanoma cells were exposed to increasing concentrations of trametinib and/or dabrafenib, either before or after separation into CD133(+) and CD133(-) subpopulations. In parental CD133-mixed lines, the percentages of CD133(+) cells increased significantly (p<0.05) after high-dose drug treatment. Presorted CD133(+) cells also exhibited significantly greater (p<0.05) IC50s for single and combination MAPKI treatment. siRNA knockdown revealed a causal relationship between CD133 and drug resistance. Microarray and qRT-PCR analyses revealed that ten of 18 ABC transport...Continue Reading

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Citations

Jan 12, 2021·Stem Cells International·Tomasz KloskowskiMarta Pokrywczyńska
Mar 17, 2020·Pathology, Research and Practice·Nazila Fathi MaroufiMohammad Nouri

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Methods Mentioned

BETA
FACS
Flow Cytometry
Reverse-Transcription PCR
biopsy
PCR
xenografts

Software Mentioned

ImageJ

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