Quantitative Proteomic Analysis of the Effects of Dietary Deprivation of Methionine and Cystine on A549 Xenograft and A549 Xenograft-bearing Mouse

Methionine (Met) and cystine (CySS) are key sulfur donors in cell metabolism and are important nutrients for sustaining tumor growth; however, the molecular effects associated with their deprivation remain to be characterized. Here, we applied a xenograft mouse model to assess the impact of their deprivation on A549 xenografts and the xenograft-bearing animal. Results show that Met and CySS deprivation inhibits A549 growth in vitro, not in vivo. Deprivation was detrimental to the xenograft-bearing mouse, as demonstrated by weight loss and renal dysfunction. Differentially expressed proteins in A549 xenograft and mouse kidneys were characterized using quantitative proteomics. Functional annotation and protein-protein interaction network analysis revealed the enriched signaling pathways, including focal adhesion (Fn1) in the A549 xenograft, and xenobiotic metabolism (Cyp2e1) and glutathione metabolism (Ggt1) in the mouse kidney. Met and CySS deprivation inhibits the migratory and invasive properties of cancer cells, as evidenced by reduced expression of the epithelial to mesenchymal transition marker N-cadherin in A549 cells in vitro. Moreover, IGFBP1 protein expression was inhibited in both A549 xenograft and mouse kidneys. This study provides the first insights into changes within the proteome profile and biological processes upon Met and CySS deprivation in a A549 xenograft mouse model.