MOLECULAR AND PHARMACOLOGICAL TARGETING OF ANGIOGENESIS FACTORS - THEEXAMPLE OF PLEIOTROPHIN

Polypeptide growth factors contribute to the development and maintenan ce of normal tissues and are essential for the growth and metastasis o f solid tumors. During tumor progression these factors function as aut ocrine stimulators of tumor cells and/or serve to recruit stromal tiss ue and blood supply to the expanding tumor. In particular, tumor-induc ed angiogenesis appears to be significant not only for local tumor gro wth but also for metastasis to distant organ sites. We purified severa l years ago the heparin-binding growth factor pleiotrophin (PTN) from the supernatants of human breast cancer cells and demonstrated that PT N can serve as an angiogenesis factor. We found the gene expressed in a number of human tumor cell lines as well as in human tumor tissues. Here we present different approaches to inhibit production and functio n of this growth factor. Finally we discuss how the experience from th is growth factor can be applied to improve our understanding of the ro le of other factors thought to contribute to tumor angiogenesis.