PPARγ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis Journal Article
| Authors: | Panigrahy, D.; Singer, S.; Shen, L. Q.; Butterfield, C. E.; Freedman, D. A.; Chen, E. J.; Moses, M. A.; Kilroy, S.; Duensing, S.; Fletcher, C.; Fletcher, J. A.; Hlatky, L.; Hahnfeldt, P.; Folkman, J.; Kaipainen, A. |
| Article Title: | PPARγ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis |
| Abstract: | Several drugs approved for a variety of indications have been shown to exhibit antiangiogenic effects. Our study focuses on the PPARγ ligand rosiglitazone, a compound widely used in the treatment of type 2 diabetes. We demonstrate, for the first time to our knowledge, that PPARγ is highly expressed in tumor endothelium and is activated by rosiglitazone in cultured endothelial cells. Furthermore, we show that rosiglitazone suppresses primary tumor growth and metastasis by both direct and indirect antiangiogenic effects. Rosiglitazone inhibits bovine capillary endothelial cell but not tumor cell proliferation at low doses in vitro and decreases VEGF production by tumor cells. In our in vivo studies, rosiglitazone suppresses angiogenesis in the chick chorioallantoic membrane, in the avascular cornea, and in a variety of primary tumors. These results suggest that PPARγ ligands may be useful in treating angiogenic diseases such as cancer by inhibiting angiogenesis. |
| Keywords: | immunohistochemistry; vasculotropin; controlled study; human cell; angiogenesis inhibitor; drug efficacy; nonhuman; antineoplastic agents; antineoplastic agent; prostate specific antigen; mouse; animal; animals; animal tissue; metastasis; animal experiment; animal model; transcription factor; antineoplastic activity; angiogenesis; physiology; transcription factors; cancer invasion; fibroblast growth factor 2; cancer inhibition; ligand; neoplasm metastasis; ligands; cattle; neoplasm invasiveness; metastasis potential; tumor growth; thiazoles; angiogenesis inhibitors; peroxisome proliferator activated receptor gamma; rosiglitazone; receptors, cytoplasmic and nuclear; metastasis inhibition; thiazole derivative; basic fibroblast growth factor; cell receptor; thiazolidinediones; capillary endothelium; 2,4 thiazolidinedione derivative; chorioallantois; troglitazone; peroxisome proliferator activated receptor agonist; 2,4 thiazolidinedione; humans; human; priority journal; article; pirinixic acid; 2,4-thiazolidinedione |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 110 |
| Issue: | 7 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2002-10-01 |
| Start Page: | 923 |
| End Page: | 932 |
| Language: | English |
| DOI: | 10.1172/JCI15634 |
| PUBMED: | 12370270 |
| PROVIDER: | scopus |
| PMCID: | PMC151148 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
