title: PPARgamma 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 PPARgamma ligand rosiglitazone, a compound widely used in the treatment of type 2 diabetes. We demonstrate, for the first time to our knowledge, that PPARgamma 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 PPARgamma ligands may be useful in treating angiogenic diseases such as cancer by inhibiting angiogenesis.
authors.affiliation: Surgical Research Laboratory, Children's Hospital, Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Dipak
authors.initials: D
authors.lastname: Panigrahy
authors.forename: Samuel
authors.initials: S
authors.lastname: Singer
authors.forename: Lucy Q
authors.initials: LQ
authors.lastname: Shen
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Butterfield
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Freedman
authors.forename: Emy J
authors.initials: EJ
authors.lastname: Chen
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Moses
authors.forename: Susan
authors.initials: S
authors.lastname: Kilroy
authors.forename: Stefan
authors.initials: S
authors.lastname: Duensing
authors.forename: Christopher
authors.initials: C
authors.lastname: Fletcher
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
authors.forename: Lynn
authors.initials: L
authors.lastname: Hlatky
authors.forename: Philip
authors.initials: P
authors.lastname: Hahnfeldt
authors.forename: Judah
authors.initials: J
authors.lastname: Folkman
authors.forename: Arja
authors.initials: A
authors.lastname: Kaipainen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006801:Humans; D008024:Ligands; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; C089946:2,4-thiazolidinedione