Metastasis is the most common cause of major morbidity and death in cancer patients. Approximately 15% of all women first diagnosed with localized breast cancer will develop metastases, mainly targeting liver, lung, bone and brain. Dissecting the mechanisms of breast cancer metastasis is important for the future design of molecular targeted therapeutics that block or target metastases and reduce the incidence and impact of metastatic disease. Oncoproteomics has proven a useful tool for identifying diagnostic and prognostic biomarkers and potential therapeutic targets. Using label free proteomic analysis, we compared the membrane protein profile of a range of breast cancer cell lines with different metastatic potential derived from a syngeneic mouse model, with the objective of identifying novel therapeutic targets.
After successful enrichment of membrane proteins from the panel of breast cancer cell lines, i.e. 4T1, 4T1.2, 4T07, 66cl4, 67NR and EMT6.5, we identified a number of pathways that were up-regulated in highly metastatic cell lines and have been previously associated with tumour progression including the PI3K-AKT pathway, Rap1, Ras signaling pathway and proteins important in platelet activation. In addition to the identification of known players in metastasis we also identified novel candidate metastasis promoter and suppressor proteins/pathways such as those involved in antigen processing and presentation, and focal adhesion. We are currently validating these novel metastasis regulators in the hope of identifying prognostic markers and novel targets for therapies aimed at preventing the expansion of secondary metastatic lesions.