Faculty Collaboration Database

Kallistatin is a new inhibitor of angiogenesis and tumor growth. Blood 2002 Nov 01;100(9):3245-52

Date

10/18/2002

Pubmed ID

12384424

DOI

10.1182/blood-2002-01-0185

Scopus ID

2-s2.0-0036839310 (requires institutional sign-in at Scopus site)   173 Citations

Abstract

Kallistatin is a unique serine proteinase inhibitor (serpin) and a heparin-binding protein. It has been localized in vascular smooth muscle cells and endothelial cells of human blood vessels, suggesting that kallistatin may be involved in the regulation of vascular function. Our previous study showed that kallistatin plays a role in neointima hyperplasia. In this study, we investigated the potential role of kallistatin in angiogenesis in vitro and in vivo. Purified human kallistatin significantly inhibited vascular endothelial growth factor (VEGF)- or basic fibroblast growth factor (bFGF)-induced proliferation, migration, and adhesion of cultured endothelial cells. Kallistatin attenuated VEGF- or bFGF-induced capillary density and hemoglobin content in subcutaneously implanted Matrigel plugs in mice. To further investigate the role of kallistatin in angiogenesis, we prepared adenovirus carrying the human kallistatin cDNA (Ad.HKBP) and evaluated the effect of kallistatin gene delivery on spontaneous angiogenesis in a rat model of hind-limb ischemia. Local kallistatin gene delivery significantly reduced capillary formation and regional blood perfusion recovery in the ischemic hind limb after removal of the femoral artery. Furthermore, a single intratumoral injection of Ad.HKBP into pre-established human breast tumor xenografts grown in athymic mice resulted in significant inhibition of tumor growth. CD31 immunostaining of tumor sections showed a decreased number of blood vessels in the kallistatin-treated group as compared to the control. These results demonstrate a novel role of kallistatin in the inhibition of angiogenesis and tumor growth.

Author List

Miao RQ, Agata J, Chao L, Chao J

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adenoviridae
Angiogenesis Inhibitors
Animals
Breast Neoplasms
Carrier Proteins
Cell Adhesion
Cell Division
Cell Movement
Cells, Cultured
DNA, Complementary
Drug Implants
Endothelial Growth Factors
Endothelium, Vascular
Female
Fibroblast Growth Factor 2
Genetic Vectors
Hindlimb
Humans
Injections, Intralesional
Intercellular Signaling Peptides and Proteins
Ischemia
Lymphokines
Male
Neovascularization, Pathologic
Neovascularization, Physiologic
Rats
Recombinant Fusion Proteins
Serpins
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Xenograft Model Antitumor Assays