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Nat Med. 2002 Sep;8(9):995-1003. Epub 2002 Aug 19.

Parathyroid hormone-related peptide is a naturally occurring, protein kinase A-dependent angiogenesis inhibitor.

Author information

1
University of California, San Diego Comprehensive Cancer Center, La Jolla, California, USA.

Abstract

Angiogenesis is a highly regulated process that results from the sequential actions of naturally occurring stimulators and inhibitors. Here, we show that parathyroid hormone-related peptide, a peptide hormone derived from normal and tumor cells that regulates bone metabolism and vascular tone, is a naturally occurring angiogenesis inhibitor. Parathyroid hormone-related peptide or a ten-amino-acid peptide from its N terminus inhibits endothelial cell migration in vitro and angiogenesis in vivo by activating endothelial cell protein kinase A. Activation of protein kinase A inhibits cell migration and angiogenesis by inhibiting the small GTPase Rac. In contrast, inhibition of protein kinase A reverses the anti-migratory and anti-angiogenic properties of parathyroid hormone-related peptide. These studies show that parathyroid hormone-related peptide is a naturally occurring angiogenesis inhibitor that functions by activation of protein kinase A.

PMID:
12185361
DOI:
10.1038/nm753
[Indexed for MEDLINE]

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