Publisher Summary This chapter describes the Ras, metastasis, and matrix metalloproteinase 9. The process of metastasis involves breakdown and penetration of intercellular matrix and basement membranes. The basement membrane in particular is a barrier to tumor invasion, intravasation, and extravasation. Type IV collagen is the predominant collagen component of the basement membrane, and type IV matrix metalloproteinase activity may contribute significantly to the metastatic process by mediating its cleavage. Ras oncogene activation has been shown to promote metastasis in many experimental tumor cell models and has been implicated in the metastatic progression of human cancers. In addition, type IV matrix metalloproteinase (MMPs) is implicated in the regulation of tumor cell proliferation both at the primary site and at the site of metastasis. The induction of metastatic behavior in cells expressing activated ras is correlated with increased MMP activity, and AP-1 is known to promote the expression of type IV MMPs. To detect metastatic cells at early time points after injection and monitor their fate and location, tumor cells can be labeled by transfection with a vector expressing green fluorescent protein (GFP) such as pEGFP-C2.