Pilot Project 2--The primary aim of this study is to develop novel molecular imaging methodology to visualize and quantify the expression and activity of tyrosine kinase growth factor receptor and mitochondria uncoupling proteins in metastasis. The Met tyrosine kinase growth factor receptor, its ligand hepatocyte and Mimp (ref), a novel Met-HGF/SF-induced protein will serve as a model. Using novel molecular imaging modalities we will analyze the effects of Met and HGF/SF overexpression on mammary tumors and metastasis formation. Subsequently, using a Tet inducible Mimp we will examine the effects of Mimp expression on Met-HGF/SF-induced metastasis. Preliminary results suggest that Mimp reduces Met-HGF/SF-induced metastasis. The combined expression of Met and Mimp which is inhibitory and its down-stream effects may shed light on the involvement of mitochondrial uncoupling activities in regulating HGF/SF-induced metastasis.
Our specific aims are: 1) to image overexpression of Met and HGF/SF in an in vitro invasion process and in tumor and metastasis formation. 2) to characterize the effect of Mimp induction on the tumorigenic/metastatic potential in in-vitro and in vivo systems. 3) to develop molecular imaging modalities for Mimp-luciferase and Mimp-DsRed in tumorigenicity and metastasis.
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