312. Human Plasminogen Kringle 5-Engineered Murine Mammary Cancer Cells Arrest Tumor Growth and Promote Long-Term Survival

Abstract

Objective: Neoangiogenesis has been strongly correlated with aggressive breast tumor growth and metastasis. However, since tumor-associated neovasculature is not of malignant origin, it retains the ability to respond physiologically to growth arrest signals and is the proposed basis for breast tumor regression in vivo. The fifth kringle (K5) domain of human plasminogen is distinct from angiostatin (K1-4), and has been shown -on its own- to act as a potent suppressor of angiogenesis. We propose that the K5 domain may serve as a potent angiostatic agent and that it may act as a useful therapeutic transgene within a breast cancer gene therapy strategy. To test this hypothesis, we have developed a K5-expressing retroviral vector, gene-modified murine DA3 mammary cells to produce soluble human K5 protein and characterized the anti-tumor potency of the de novo produced K5 peptide in vivo.