Angiogenic Assays and Antiangiogenic Therapy

The long range goals of this proposal are the establishment of accurate, sensitive and specific asstumor markers and to develop novel anti-angiogenic, anti-tumor therapy. Phase I focuses on the oncogand its product (PTN), a recently described growth and angiogenic factor. Ptn is expressed in high lhighly vascularized breast cancer and its product PTN is released into conditioned media from culturPTN thus may be a marker for angiogenic tumors and, control its angiogenic properties, PTN may be aneffective anti-tumor therapy. Two essential steps to the long-range goals of this proposal are incluplanned to develop and characterize anti-Ptn monoclonal antibodies for use in specific and sensitiveto identify and monitor angiogenic tumors; it is planned to generate a chimeric PTN/pseudomonas exoteffectively the cells needed for angiogenesis in support of tumor cell growth. Nude mice with tumorsMMTV promotor/Ptn transgenic mice that target expression of Ptn to breast epithelial cells are availthe reagents generated. Human patient populations and the samples for subsequent analysis have beenII. The experiments in this proposal form the basis for preparation of new diagnostic kits to detectangiogenesis and for development of potentially novel anti-angiogenic therapeutic reagents in hemato