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

Abstract

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.

• Authors: Young Eun Kim, Hyo Jin Jeon, Dahee Kim, Sun Young Lee, Ki Young Kim, Jongki Hong, Pil Jae Maeng, Kwang-Rok Kim, Dukjin Kang
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 13255 (09 05 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 30185973 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gelsolin
• Heterocyclic Compounds, 3-Ring
• Proteome
• XAV939
• L-Lactate Dehydrogenase
• LDHA protein, human

Topics

• Cell Communication (drug effects)
• Cell Culture Techniques (methods)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (metabolism)
• Gelsolin (metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Heterocyclic Compounds, 3-Ring (pharmacology)
• Humans
• L-Lactate Dehydrogenase (metabolism)
• Proteome (drug effects)
• Proteomics (methods)
• Spheroids, Cellular