Pancreatic cancer kills more than 200 thousand people worldwide every year. Also, pancreatic cancer is considered one of the most aggressive adenocarcinomas and of difficult diagnosis since it develops silently and presents a high genetic complexity. Consequently, the diagnostic is often late, when the pancreatic cancer has already metastasized and the treatment has only palliative purposes. The most frequent genetic alterations observed in pancreatic cancer are related to mutations in KRAS oncogene and CDKN2A, TP53, SMAD4 and BRCA2 tumor suppressor genes. In addition to these known frequent mutations, growth factors such as TGB- ² and EGF play important roles in pancreatic cancer progression and metastasis. Interestingly, TGB- ² and EGF are also inducers of the Epithelial to Mesenchymal Transition (EMT), in which epithelial cells lose their intracellular contacts and acquire migratory abilities. Therefore, EMT is considered one of the mechanisms responsible for tumor progression and metastasis in adenocarcinomas in addition of being correlated to the process of generating cancer stem cells. Here in our study, we will perform an in-depth proteomic qualitative and quantitative analysis based on stable isotope labeling in cell culture (SILAC) followed by cellular and protein fractionation in order to elucidate the alterations promoted by the induction of EMT in pancreatic cancer cell lines. Pancreatic cancer cells will be treated with TGB- ² and EGF in order to induce migratory and invasive characteristics achieved during EMT and that can be representative of a controlled metastatic process. With this approach we will pursue the identification of candidate proteins that can be further evaluated as potential diagnostic or therapeutic targets for metastatic disease. Combined to the dataset on pancreatic cancer we recently published, we intend to select for candidate biomarkers for validation in clinical samples from pancreatic cancer patients.
|Effective start/end date||1/04/12 → 31/07/16|
- Fundação de Amparo à Pesquisa do Estado de São Paulo