Cisplatin resistant spheroids model clinically relevant survival mechanisms in ovarian tumors
S2 Table. List of genes significantly differentially expressed between OVCAR-8R and OVCAR-8 spheroids (762.5Kb)
Messerli, Shanta M.
Miller, Daniel H.
Medina, Jamie E.
Hamilton, Joshua W.
Messerli, Mark A.
Brodsky, Alexander S.
MetadataShow full item record
The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05) (S2 Table). Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.
© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS 11 (2016): e0151089, doi: 10.1371/journal.pone.0151089 .
The following license files are associated with this item:
Showing items related by title, author, creator and subject.
Menachery, Anoop; Graham, David M.; Messerli, Shanta M.; Pethig, Ronald; Smith, Peter J. S. (2010-06-03)The ability to isolate and accurately position single cells in three dimensions is becoming increasingly important in many areas of biological research. We describe the design, theoretical modeling and testing of a novel ...
Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel exposure and correlate with reduced praziquantel susceptibility Messerli, Shanta M.; Kasinathan, Ravi S.; Morgan, William; Spranger, Stefani; Greenberg, Robert M. (2009-04-28)One potential physiological target for new antischistosomals is the parasite's system for excretion of wastes and xenobiotics. P-glycoprotein (Pgp), a member of the ATP-binding cassette superfamily of proteins, is an ...
Ion trapping with fast-response ion-selective microelectrodes enhances detection of extracellular ion channel gradients Messerli, Mark A.; Collis, Leon P.; Smith, Peter J. S. (2008-11)Previously, functional mapping of channels has been achieved by measuring the passage of net charge and of specific ions with electrophysiological and intracellular fluorescence imaging techniques. However, functional ...