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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042229-03
Application #
3183214
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1988-04-01
Project End
1991-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Roghani, Monireh; Moscatelli, David (2007) Prostate cells express two isoforms of fibroblast growth factor receptor 1 with different affinities for fibroblast growth factor-2. Prostate 67:115-24
Richard, C; Roghani, M; Moscatelli, D (2000) Fibroblast growth factor (FGF)-2 mediates cell attachment through interactions with two FGF receptor-1 isoforms and extracellular matrix or cell-associated heparan sulfate proteoglycans. Biochem Biophys Res Commun 276:399-405
Liuzzo, J P; Moscatelli, D (1996) Human leukemia cell lines bind basic fibroblast growth factor (FGF) on FGF receptors and heparan sulfates: downmodulation of FGF receptors by phorbol ester. Blood 87:245-55
Roghani, M; Mohammadi, M; Schlessinger, J et al. (1996) Induction of urokinase-type plasminogen activator by fibroblast growth factor (FGF)-2 is dependent on expression of FGF receptors and does not require activation of phospholipase Cgamma1. J Biol Chem 271:31154-9
Chow, R L; Roux, G D; Roghani, M et al. (1995) FGF suppresses apoptosis and induces differentiation of fibre cells in the mouse lens. Development 121:4383-93
Richard, C; Liuzzo, J P; Moscatelli, D (1995) Fibroblast growth factor-2 can mediate cell attachment by linking receptors and heparan sulfate proteoglycans on neighboring cells. J Biol Chem 270:24188-96
Rifkin, D B; Moscatelli, D; Roghani, M et al. (1994) Studies on FGF-2: nuclear localization and function of high molecular weight forms and receptor binding in the absence of heparin. Mol Reprod Dev 39:102-4;discussion 104-5
Moscatelli, D (1994) Autocrine downregulation of fibroblast growth factor receptors in F9 teratocarcinoma cells. J Cell Physiol 160:555-62
Roghani, M; Mansukhani, A; Dell'Era, P et al. (1994) Heparin increases the affinity of basic fibroblast growth factor for its receptor but is not required for binding. J Biol Chem 269:3976-84
Huang, Y Q; Li, J J; Moscatelli, D et al. (1993) Expression of int-2 oncogene in Kaposi's sarcoma lesions. J Clin Invest 91:1191-7

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