Cure Osteosarcoma Lung Metastasis by Disrupting Tumor VCAM-1 Signaling with Macrophages
Background: Osteosarcoma (OS) is the most common aggressive primary bone cancer in the pediatric and adolescent population. Half of all new cases of OS diagnosed in the U.S. occur in children and young adults, and about 20% of these patients have metastatic spread, while others developed lung metastasis after initiation of therapy. Lung metastasis in OS responds poorly to conventional chemotherapy, which accounts for most of the mortality. Recent exciting scientific development implicates the immune system as an important new armamentarium in a novel approach to control or reduce OS metastasis through modulating the function of an immune cell called macrophages, and a molecule called VCAM-1. Project Goal: Here we propose to use cutting-edge imaging technology to directly evaluate how communications between tumor cells and lung macrophages can be affected positively or negatively by modulating VCAM-1 function. Success in this effort will confirm the role VCAM-1 plays in OS metastasis in vivo as a first step towards clinical translation and foster the development of new therapeutic approaches to combat metastatic OS. As agents to deplete macrophages and block VCAM-1 function are already in clinical trials, we plan to use data collected in this proposal to seek further grant support through NIH R01 mechanisms in late 2016 or early 2017, and will begin to develop targeting agents for Phase I clinical trials in OS.