Premium
Deregulation of tumor angiogenesis and blockade of tumor growth in PPARβ‐deficient mice
Author(s) -
MüllerBrüsselbach Sabine,
Kömhoff Martin,
Rieck Markus,
Meissner Wolfgang,
Kaddatz Kerstin,
Adamkiewicz Jürgen,
Keil Boris,
Klose Klaus J,
Moll Roland,
Burdick Andrew D,
Peters Jeffrey M,
Müller Rolf
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601803
Subject(s) - biology , blockade , angiogenesis , cancer research , neovascularization , microbiology and biotechnology , receptor , genetics
The peroxisome proliferator‐activated receptor‐β (PPARβ) has been implicated in tumorigenesis, but its precise role remains unclear. Here, we show that the growth of syngeneic Pparb wild‐type tumors is impaired in Pparb −/− mice, concomitant with a diminished blood flow and an abundance of hyperplastic microvascular structures. Matrigel plugs containing pro‐angiogenic growth factors harbor increased numbers of morphologically immature, proliferating endothelial cells in Pparb −/− mice, and retroviral transduction of Pparb triggers microvessel maturation. We have identified the Cdkn1c gene encoding the cell cycle inhibitor p57 Kip2 as a PPARβ target gene and a mediator of the PPARβ‐mediated inhibition of cell proliferation, which provides a possible mechanistic explanation for the observed tumor endothelial hyperplasia and deregulation of tumor angiogenesis in Pparb −/− mice. Our data point to an unexpected essential role for PPARβ in constraining tumor endothelial cell proliferation to allow for the formation of functional tumor microvessels.