GLYCOMARKER · PROTEOMICS BASED IDENTIFICATION OF BIOMARKERS AND CLEAVAGE PRODUCTS IN PANCREATIC CANCER USING GLYCO-CAPTURE TECHNOLOGY

In cancer biology, primary tumours and metastasis are embedded in a microenvironment comprised of cells such as tumour associated macrophages and cancer-associated fibroblasts. Tumour and stroma derived cytokines form a paracrine loop of mutual activation, often resulting in elevated tumour aggressiveness. Interestingly, numerous studies have shown that altered protein glycosylation is a hallmark event of carcinogenesis. In many cases, tumour progression is accompanied by several parameters which include changes in the extent of glycosylation of proteins as well as the carbohydrate structure, increased level of blood glycoproteins as well as altered glycosylation of cell surface glycolipids, membrane-associated glycoproteins and secreted glycoproteins. Both N- and O-glycosylated glycoproteins have been shown to be modified in a wide range of cancers and hence have potential as novel biomarkers for detection and surveillance of the disease. Thus, it is not surprising that many existing cancer biomarkers (e.g. Her2/neu in breast cancer, CA125 in ovarian cancer, prostate specific antigen (PSA) in prostate cancer, CEA and CA 19-9 in colorectal cancer) are glycoproteins. Despite the recent advancement in the biomarker discovery tools, however, to date the glycoproteome has not been extensively studied and thus used to mine potential biomarkers due to technical complexity. The characterisation of a glycoprotein as a biomarker for monitoring of tumour growth as well as cancer progression has the advantage that both the protein and glycan moieties contain valuable information. Together with host institute, I aim to develop novel methods for the capture/enrichment and thus identification of cancer-associated glycoproteins from pancreatic cancer cells. This approach will allow us to uncover pivotal proteolytic processing events of cell surface and secreted proteins, which further highlights the importance and elucidate the regulation of tumor-stroma interactions.