ABSTRACT
BACKGROUND: Solid tumors contain various components that together form the tumor microenvironment. Cancer associated fibroblasts (CAFs) are capable of secreting and responding to signaling molecules and growth factors. Due to their role in tumor development, CAFs are considered as potential therapeutic targets. A prominent tumor-associated signaling molecule is transforming growth factor ß (TGFß), an inducer of epithelial-to-mesenchymal transition (EMT). The differential action of TGFß on CAFs and ETCs (epithelial tumor cells) has recently gained interest. Here, we aimed to investigate the effects of TGFß on CAFs and ETCs at the proteomic level. METHODS: We established a 2D co-culture system of differentially fluorescently labeled CAFs and ETCs and stimulated this co-culture system with TGFß. The respective cell types were separated using FACS and subjected to quantitative analyses of individual proteomes using mass spectrometry. RESULTS: We found that TGFß treatment had a strong impact on the proteome composition of CAFs, whereas ETCs responded only marginally to TGFß. Quantitative proteomic analyses of the different cell types revealed up-regulation of extracellular matrix (ECM) proteins in TGFß treated CAFs. In addition, we found that the TGFß treated CAFs exhibited increased N-cadherin levels. CONCLUSIONS: From our data we conclude that CAFs respond to TGFß treatment by changing their proteome composition, while ETCs appear to be rather resilient.
