Tumor growth is dependent on the development of an adequate blood supply. Tumors will not grow beyond a limited size until they are vascularized. Once vascularization is established, tumor growth increases rapidly. Several types of tumors have been shown a elaborate a soluble factor (called an angiogenic factor) which will stimulate capillaries in the surrounding vascular system to form sprouts of new vessels. These new capillaries grow toward the source of angiogenic factor and eventually invade the tumor, thereby establishing a blood supply to the tumor. In addition, several non-tumorous tissues which are undergoing rapid growth, such as placenta, have also been shown to contain angiogenic factors. We have isolated an angiogenic factor from human placenta and have identified it as basic fibroblast growth factor (bFGF). We have identified receptors for this molecule on several cell lines. We now propose to purify the bFGF receptor and establish its amino acid sequence by partial protein sequencing and by isolating a cDNA clone and identifying the nucleotide sequence of the clone. We also propose to raise antibodies to the receptor and to use these antibodies to investigate whether the receptor is phosphorylated as a result of its interaction with bFGF. Finally, we propose to identify the region(s) of basic fibroblast growth factor that interact with the receptor by investigating the ability of peptides which represent portions of the amino acid sequence of bFGF to complete for the binding of bFGF to the receptor. These studies will characterize aspects of the bFGF-receptor interaction and may give us insight into the method of transduction of the angiogenic factor signal into a cellular response.
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