The long range goals of this proposal are the establishment of accurate, sensitive and specific assays for angiogenic tumor markers and to develop novel anti-angiogenic, anti-tumor therapy. Phase I focuses on the oncogene pleiotrophin (Ptn) and its product (PTN), a recently described growth and angiogenic factor. Ptn is expressed in high levels in cells from highly vascularized breast cancer and its product PTN is released into conditioned media from cultured breast cancer cells. PTN thus may be a marker for angiogenic tumors and, control its angiogenic properties, PTN may be an important target for effective anti-tumor therapy. Two essential steps to the long-range goals of this proposal are included in Phase I. It is planned to develop and characterize anti-Ptn monoclonal antibodies for use in specific and sensitive radioimmunoassay kits to identify and monitor angiogenic tumors; it is planned to generate a chimeric PTN/pseudomonas exotoxin molecule to kill effectively the cells needed for angiogenesis in support of tumor cell growth. Nude mice with tumors that express PTN and MMTV promotor/Ptn transgenic mice that target expression of Ptn to breast epithelial cells are available as models to test the reagents generated. Human patient populations and the samples for subsequent analysis have been identified for Phase II. The experiments in this proposal form the basis for preparation of new diagnostic kits to detect and monitor tumor angiogenesis and for development of potentially novel anti-angiogenic therapeutic reagents in hematological diseases.National Cancer Institute (NCI)
