Osteosarcoma is the most common bone tumor in dogs, with increased risk for large and giant breeds. Osteosarcoma is an aggressive disease, and most dogs succumb to metastatic disease in the lungs, regardless of treatment. Tumors survive and thrive by reprogramming the host immune response to ignore abnormal tumor cells and even promote their growth and spread to other sites. How tumors, including osteosarcoma, exert control over the immune system is not well-understood. Preliminary work from the investigators’ laboratory shows that canine osteosarcoma cells reprogram macrophages to increase the production of signals that have been associated with aggressive and metastatic human cancers. This study will determine whether canine osteosarcoma cells induce these changes through classic signaling molecules called cytokines, or through small lipid-bound cellular fragments called extracellular vesicles. Next, they will determine whether the signals released by macrophages stimulate growth or aggressive behavior in the osteosarcoma cells themselves. These studies will provide important insight into how canine osteosarcoma controls macrophages, with potential implications in the development of new therapies that slow or even halt tumor growth and spread.