Grant: Operating Grant

The liver is the major site of metastasis for some of the most common human malignancies, particularly cancers of the GI tract such as colorectal carcinoma. While improvements in surgical techniques have significantly improved disease outcome, most patients with liver metastases still die of their disease. To improve these statistics and prevent liver metastasis, a better understanding of the underlying biology is essential. Our previous work identified the liver microenvironment, in particular the host inflammatory response as a promoter of the early stages of metastasis and implicated the receptor for the growth factor IGF-I in the regulation of this response. Here we propose to continue our studies on the crosstalk between these two systems as well as to test the effect of anti-inflammatory drugs on metastasis of human tumor cells. The results should provide further insight into the interaction between tumor cells and their microenvironment and determine the therapeutic benefit of several novel treatment strategies.