Grant: Operating Grant

Autocrine motility factor (AMF) and its receptor, gp78/AMFR, promote tumor cell motility and metastasis and are closely associated with malignancy in various cancers. When AMF binds to gp78/AMFR it is efficiently and selectively taken up by cancer cells. We are exploring whether internalization of AMF can be used to deliver chemotherapeutic agents selectively to cancer cells. We have developed a novel targeted therapeutic for cancer, called AMF-paclitaxel. By linking AMF to paclitaxel (an anti-cancer drug used clinically for cancer treatment) we expect to deliver this chemotherapeutic drug more selectively to cancer cells, but not normal body cells. This should increase the efficacy and reduce toxic side effects of cancer treatment with paclitaxel. In this grant, we propose to link AMF to the clinically relevant isotope (99m-Technetium) and determine whether it can be used to visualize cancer cells in the body. We will assess whether AMF-paclitaxel prevents tumor growth, induces tumor regression and prolongs survival in mice bearing human tumors. We will also generate cancer cells expressing reduced levels of gp78/AMFR to test the effect of gp78/AMFR expression on tumor growth and metastasis and also for AMF-mediated tumor cell targeting. If successful, these studies will suggest that AMF is an effective delivery agent for human cancers and lead to its development for clinical application.