Tumor-stromal interactions in colon cancer: The role of EGFR; COX-2 and bile acids
My lab seeks to understand tumor-stromal interactions involved in the initiation and progression of colorectal (CRC) to liver metastasis. Using an in vitro system which simulates in vivo conditions, we seek to determine the mechanism by which bile acids stimulate release of EGFR ligands from the cell surface and activate the EGFR and COX-2 expression in polarized epithelial CRC cells. This work is complemented using an in vivo mouse model of liver metastasis. With our mouse model we are also trying to identify genes involved in the metastasic process of CRC using genomic and proteomic approaches with microarray and imaging mass spectrometry as well as a reversible gene-trap method of identifying tumor suppresor genes involved in metastasis. In addition we are studying different methods of in vivo small animal imaging of tumors and their metastasis using In Vivo Bioluminescence Imaging with a luciferase reporter, CT scanning and PET scanning through a mutant dopamine receptor. This work is further translated into the clinical forum through several clinical trials involving COX-2 inhibitors, EGFR inhibitors and angiogenesis inhibitors in patients with CRC. Tumors obtained from patients with CRC are further analyzed to help determine the mechanisms by which these agents function and also to develop a comprehensive genomic and proteomic profile of tumors to identify the molecular signatures of these tumors.