Modeling Synovial Sarcoma Metastasis in the Mouse: PI3'-Lipid Signaling and Inflammation

Background

Synovial sarcomas are the most prevalent soft tissue sarcomas to affect adolescents and young adults, yet they have a very poor prognosis when metastatic. One reason research has been difficult was the inability to produce an animal model that reproduced accurate metastasis without change in histology of the tumor. Previous research done at the Huntsman Cancer Institute has led to the development of that accurate animal model, which allows for much better insight into the tumor's characteristics and makeup. This cancer type has been highly associated with PI3'-lipid signaling, PTEN silencing, and the SS18-SSX fusion oncoprotein. Deficiency in PTEN was shown to increase angiogenesis, promote inflammation, and allow for pulmonary metastasis. PTEN deficiency also led to heavy recruitment of macrophages and neutrophils into the tumor tissue. This drastic increase in immune cells is seen in another sarcoma type, leiomyosarcoma, and is linked to a poor prognosis, lending the link between PTEN and these immune cells as a future direction of investigation. Another tumor characteristic is the PI3'-lipid signaling and its resultant increase in inflammatory response, again leading to the recruitment of the same macrophages and neutrophils. This is due to an increase of a CSF1 receptor in both the macrophages and vascular endothelial cells allowing for passage of the macrophages into the connective tissues.

Project Goal

The direction of this current research is to explore the relationship of these immune cells and their link to poor prognosis, further examine PI3' signaling and PTEN roles in tumor metastasis, and test possible anti-metastatic mechanisms.