Proteomic Comparison of 3D and 2D Glioma Models Reveals Increased HLA-E Expression in 3D Models is Associated with Resistance to NK Cell-Mediated Cytotoxicity

Jeon

et al. 2018

Sci Rep

Recently there has been a growing interest in three-dimensional (3D) cell culture systems for drug discovery and development. These 3D culture systems better represent the in vivo cellular environment compared to two-dimensional (2D) cell culture, thereby providing more physiologically reliable information on drug screening and testing. Here we present the quantitative profiling of a drug-induced proteome in 2D- and 3D-cultured colorectal cancer SW480 cells using 2D nanoflow liquid chromatography-tandem mass spectrometry (2D-nLC-MS/MS) integrated with isobaric tags for relative and absolute quantitation (iTRAQ). We identified a total of 4854 shared proteins between 2D- and 3D-cultured SW480 cells and 136/247 differentially expressed proteins (up/down-regulated in 3D compared to 2D). These up/down-regulated proteins were mainly involved in energy metabolism, cell growth, and cell-cell interactions. We also investigated the XAV939 (tankyrase inhibitor)-induced proteome to reveal factors involved in the 3D culture-selective growth inhibitory effect of XAV939 on SW480 cells. We identified novel XAV939-induced proteins, including gelsolin (a possible tumor suppressor) and lactate dehydrogenase A (a key enzyme of glycolysis), which were differentially expressed between 2D- and 3D-cultured SW480 cells. These results provide a promising informative protein dataset to determine the effect of XAV939 on the expression levels of proteins involved in SW480 cell growth.

Section: Resultsmentioning

confidence: 87%

Quantitative Proteomic Analysis of 2D and 3D Cultured Colorectal Cancer Cells: Profiling of Tankyrase Inhibitor XAV939-Induced Proteome

Jeon

et al. 2018

Sci Rep

European Journal of Pharmaceutics and Biopharmaceutics

“…found in tumors often heighten resistance to radiotherapy and chemotherapy [80][81][82]. Glioblastoma spheroids harbor hypoxic cores where metabolic pathways, including those involving lipids, are changed [4,[83][84][85].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Zhang

Cui

Amiri

et al. 2016

a b s t r a c tIncreased lipid droplet number and fatty acid synthesis allow glioblastoma multiforme, the most common and aggressive type of brain cancer, to withstand accelerated metabolic rates and resist therapeutic treatments. Lipid droplets are postulated to sequester hydrophobic therapeutic agents, thereby reducing drug effectiveness. We hypothesized that the inhibition of lipid droplet accumulation in glioblastoma cells using pyrrolidine-2, a cytoplasmic phospholipase A2 alpha inhibitor, can sensitize cancer cells to the killing effect of curcumin, a promising anticancer agent isolated from the turmeric spice. We observed that curcumin localized in the lipid droplets of human U251N glioblastoma cells. Reduction of lipid droplet number using pyrrolidine-2 drastically enhanced the therapeutic effect of curcumin in both 2D and 3D glioblastoma cell models. The mode of cell death involved was found to be mediated by caspase-3. Comparatively, the current clinical chemotherapeutic standard, temozolomide, was significantly less effective in inducing glioblastoma cell death. Together, our results suggest that the inhibition of lipid droplet accumulation is an effective way to enhance the chemotherapeutic effect of curcumin against glioblastoma multiforme.

“…However, this result was attributed to a decrease in heat shock protein 70 (HSP70) expression and associated defective tumor antigen presentation 45 . Glioma spheroids also appeared to have an increased resistance to natural killer (NK) cell cytotoxicity compared to glioma cells grown in 2D monolayers 46 . These findings support the importance of using 3D culture for developing in vitro models of tumor-immune cell interactions.…”

Section: Biomaterials To Create 3d Tumor Modelsmentioning

confidence: 99%

Biomaterials and emerging anticancer therapeutics: engineering the microenvironment

2015

The microenvironment is increasingly recognized to play key roles in cancer, and biomaterials provide a means to engineer microenvironments both in vitro and in vivo to study and manipulate cancer. In vitro cancer models using 3D matrices recapitulate key elements of the tumor microenvironment and have revealed new aspects of cancer biology. Cancer vaccines based on some of the same biomaterials have, in parallel, allowed for the engineering of durable prophylactic and therapeutic anticancer activity in preclinical studies, and some of these vaccines have moved to clinical trials. The impact of biomaterials engineering on cancer treatment is expected to further increase in importance in the years to come.