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REGULATION OF FGF 2 MEDIATED ANGIOGENESIS BY SPARC

Award Number: K01CA089689
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/01/2001
PERIOD OF PERFORMANCE END DATE: 02/28/2005

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REGULATION OF FGF 2 MEDIATED ANGIOGENESIS BY SPARC - DESCRIPTION (Applicant's Description): This proposal is submitted by Kouros Motamed, an Associate Investigator in the laboratory of Dr. Helene Sage, formerly at the University of Washington, Seattle and currently at the Hope Heart Institute, Seattle. Dr. Motamed is also associated with the Biology of the Artery Wall Program Project at the University of Washington. He has a strong molecular biology background with a focus on signal transduction. Over the last several years, Dr. Motamed has gained expertise in vascular biology, growth factors and their signal transduction, and the extracellular matrix (ECM) protein SPARC (secreted protein acidic and rich in cysteine). The KO1 award will enable Dr. Motamed to advance to an Assistant Member position ( e quivalent to Assistant Professor) which will be requisite for his development as an independent scientist at a University medical center, his first career preference. This research plan wi11 test the hypothesis that SPARC abrogates the angiogenic response of vascular endothelial cells (EC) to basic fibroblast growth factor(bFGF or FGF-2)in vitro and in vivo through mechanisms other than a direct molecular interaction with the growth factor. Our hypothesis is based on the following premises: a) FGF-2 stimulates proliferation and migration of EC in vitro, and b) SPARC is a modulator of cell adhesion, activity of angiogenic growth factors, cell cycle progression, matrix proteases, and ECM production. We will determine the mechanism by which SPARC inhibits FGF-2-stimulated proliferation and migration of human microvascular EC (HMVEC) through antagonism of the function of its high-affinity FGF receptor(FGFR)-1. We will test whether SPARC a) regulates FGFR-1 levels, b) suppresses FGFR-1-mediated downstream effectors, or c) inhibits the co- receptor function of FGF-2 low-affinity receptors. We wi11 also determine whether microvascular EC isolated from SPARC-null animals have higher rates of basal and FGF-2-stimulated proliferation, migration, or in vitro angiogenesis relative to wild type counterparts and whether such changes can be rescued by provision of exogenous SPARC. To corroborate our hypothesis and findings in vitro, we will determine whether SPARC inhibits FGF-2-mediated angiogenesis in vivo by the use of a quail chorioallantoic membrane model, and by examining whether SPARC-null mice display a faster rate of neovascularization in response to wound injury in a subcutaneous sponge model. Angiogenesis is requisite for the growth and metastas is of solid tumors. Modulation of EC adhesion, proliferation, and migration influences both tumor progression and angiogenesis. Insights achieved from this study on the mechanisms by which a matrix-associated protein inhibits FGF-2-stimulated blood vessel formation may lead to new approaches for treating certain cancers.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2004 ( Subtotal = $147,115 )
2004	2004	MEDICAL COLLEGE OF GEORGIA, RESEARCH INSTITUTE	RESEARCH INSTITUTE	AUGUSTA	GA	30912	RICHMOND	USA	Cancer Research Manpower	000	5	4/16/2004	NON-COMPETING CONTINUATION	$147,115
														Subtotal = $147,115

Issue Date FY: 2003 ( Subtotal = $145,598 )
2003	2003	MEDICAL COLLEGE OF GEORGIA, RESEARCH INSTITUTE	RESEARCH INSTITUTE	AUGUSTA	GA	30912	RICHMOND	USA	Cancer Research Manpower	000	4	6/5/2003	NON-COMPETING CONTINUATION	$145,598
														Subtotal = $145,598

Issue Date FY: 2002 ( Subtotal = $144,126 )
2002	2002	THE HOPE HEART INSTITUTE	556 18TH AVENUE	SEATTLE	WA	98122	KING	USA	Cancer Research Manpower	000	2	2/19/2002	NON-COMPETING CONTINUATION	$144,126
														Subtotal = $144,126

Issue Date FY: 2001 ( Subtotal = $124,632 )
2001	2001	THE HOPE HEART INSTITUTE	556 18TH AVENUE	SEATTLE	WA	98122	KING	USA	Cancer Research Manpower	000	1	2/14/2001	NEW	$124,632
														Subtotal = $124,632

Grand Total All Awards = $561,471

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REGULATION OF FGF 2 MEDIATED ANGIOGENESIS BY SPARC

Award Number: K01CA089689

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/01/2001

PERIOD OF PERFORMANCE END DATE: 02/28/2005

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