COMP/TSP-1, COMP/TSP-2 and other TSP chimeric proteins

摘要

Tumors attract blood vessels in order to grow by a process called angiogenesis. The relative quantity of stimulators and inhibitors is an important determining factor for the initiation of angiogenesis. Thrombospondins-1 and -2 are adhesive glycoproteins that have the ability to inhibit angiogenesis. This inhibiting activity has been mapped to the type 1 repeats of TSP-1 and TSP-2. The invention includes chimeric proteins that contain anti-angiogenic portions of TSP-1, TSP-2, endostatin, angiostatin, platelet factor 4, or prolactin, linked to a portion of the N-terminal region of human cartilage oligomeric matrix protein (COMP) that allows formation of pentamers. Also described herein are the nucleic acid molecules, vectors, and host cells for expressing and producing these chimeric proteins. Further embodiments of the invention include methods to treat humans or other mammals with anti-angiogenic proteins to reduce tumor size or rate of growth. Since the type 1 repeat region of TSP-1 and TSP-2 reportedly inhibits HIV infection, chimeric proteins comprising these repeats may also be used for this purpose, as well as to inhibit angiogenesis.