Role of insulin-like growth factor-II binding protein-2 (IGFBP-2) in colorectal cancer biology

The Gordon laboratory seeks to understand the role of insulin-like growth factor-II (IGF-II) binding protein-2 (IGFBP-2) in colorectal cancer biology. Recent work by this group has demonstrated that cathepsin-L is the dominant protease regulating IGFBP-2 proteolysis in intestinal epithelial crypt cells and that the carboxyl terminus of IGFP-2 is endocytosed with activation of the IGF receptor. These findings suggest a positive regulatory role for cathepsin-L and IGFBP-2 in crypt cell biology.

More recently, Dr Gordon's group has discerned that colorectal cancer cell lines commonly have aberrant proteolytic processing of IGFBP-2 and in particular, metastatic-derived lineages are found to have high abundances of IGFBP-2 carboxyl antigen in their cytoplasm. The difficulty with this model is that cell lines often acquire additional mutations in the process of surviving repeated passages and so Dr Gordon has initiated a collaboration with Dr Charles Freil for the purpose of investigating IGFBP-2 proteolysis in both primary and metastatic colon cancer specimens. Future work will involve utilization of the Biostatistical core and the Biomolecular Research Facility as the search for alternative IGFBP-2 proteases in colorectal cancer progression proceeds.