PROTEOMICS IDENTIFICATION OF INTRACELLULAR AND SECRETED PROTEINS INVOLVED IN METASTASIS FROM A PAIR OF ISOGENIC COLORECTAL CANCER CELL LINES

Abstract

Colorectal cancer is the fourth most common cause of cancer deaths and the high mortality rate is mostly ascribed to liver metastasis. To address the clinical needs in colorectal cancer metastasis management, we applied proteomics to identify intracellular and secreted proteins differentially expressed in the colon adenocarcinoma cell line HCT-116 and its metastatic derivative, E1. Drebrin (DBN1), an actin-binding protein not previously known to be involved in colorectal cancer metastasis, was found to be overexpressed in E1, and was also further validated using immunohistochemistry on patient tissues. Subsequently, we analysed the HCT-116 and E1 secretomes to search for novel biomarkers for prognosis and monitoring. After enriching for secreted glycoproteins using multi-lectin affinity chromatography, we observed the up-regulation of Laminin subunit beta-1 (LAMb1) in the E1 secretome. LAMb1 levels were also significantly higher in patient serum samples as compared to control sera, and could discriminate between colorectal cancer patients from controls.