The long-term objectives of the research are to determine the efficacy of solubilized components of the leptomeningeal extracellular matrix in treating malignant brain tumors. Phase I feasibility studies will concentrate on: (1) preparing and characterizing fibronectin from human leptomeningeal fibroblasts, (2) using that fibronectin to determine whether it can inhibit cells from causing tumors by in vitro treatment of the cells prior to injecting them, (3) whether it, like the ECM itself, can cause glioma cells to redifferentiate, and if so, to become less able to grow into tumors in vivo, and (4) developing a simple mouse model system for studying metastasis within the CNS.Awardee's statement of the potential commercial applications of the research:If studies prove positive, we will produce a biotherapeutic agent to: (1) treat inoperable malignant brain tumors using a stereotactic technic, and (2) apply to the wound site of brain tumor resections, to prevent possible micrometastic reattachment. Based on current knowledge, the agent is expected to normalize malignant cells not accessible to surgical removal, and to inhibit metastatic spread.National Cancer Institute (NCI)