3D_HOST(TM): A novel three-dimensional adaptive in vitro system to study extravasated human metastatic prostate cancer cell recruitment of human vascular endothelium

Neovascularization of primary prostate adenocarcinoma (PCa) has been well characterized; to our knowledge neovascularization of PCa metastases generated via extravasating AICs has not been examined. The successful growth of the metastases requires perfusion of the tumor mass similar but different to that of the primary tumor. The question arises as to which mechanisms are used. Model systems have been designed to study primary angiogenesis. No model system exists to study neovascularization of PCa metastases generated via extravasating AICs. We have developed a working three-dimensional model, which combines previous versions of invasion assays into one practical as well as adaptive in vitro system. It includes a “host compartment” made of collagen type I, in order to mimic the in vivo site of prostate cancer metastases-induced angiogenesis. Light microscopy analysis show that translocated endothelial cells survive, form clusters and tube-like structures within the collagen gel.; We have set the stage for a new era in cancer biology and medical oncology. 3D_HOST™ for the first time, opens both a morphological as well as a molecular window into the events following the extravasation of a human metastatic cancer cell into a target organ or tissue. We envision the identification of both clinical as well as biological targets within these post-extravasation events, that will help us understand the underlying mechanisms operating at this stage and therapies designed to stop and/or prevent the development and growth of metastases.