Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is known to influence vessel permeability. Members of the Steele Laboratory have recently demonstrated that non-neoplastic stromal cells are important contributors of intratumoral VEGF. Moreover, these cells are motile and localize with angiogenic vessels. At the moment, we do not have an understanding of how stromal cells migrate to angiogenic vessels, nor do we know the functional significance of this event. By better understanding these issues, we could propose new methods for disrupting tumor angiogenesis. This research proposal documents how I will use my previous and newly acquired skills with multiphoton microscopy and tissue transport to elucidate the role of tumor-stromal cell interactions from both a mechanistic and functional perspective. Namely, using transgenic mice which express GFP under the control of the VEGF promoter, I will determine: (1) how VEGF-expressing cells come to localize with angiogenic vessels; and (2) the impact of the proximity of these cells upon vessel permeability both within the tumor and in a controlled 3D tissue mimetic.