Therapeutic Implications of PPARgamma in Human Osteosarcoma

Overview

Journal PPAR Res

Publisher Wiley

Date 2010 Feb 26

PMID 20182546

Citations 21

Authors

Eric R Wagner

Bai-Cheng He

Liang Chen

Guo-Wei Zuo

Wenli Zhang

Qiong Shi

Qing Luo

Xiaoji Luo

Bo Liu

Jinyong Luo

Farbod Rastegar

Connie J He

Yawen Hu

Barrett Boody

Hue H Luu

Tong-Chuan He

Zhong-Liang Deng

Rex C Haydon

Affiliations

Soon will be listed here.

Abstract

Osteosarcoma (OS) is the most common nonhematologic malignancy of bone in children and adults. Although dysregulation of tumor suppressor genes and oncogenes, such as Rb, p53, and the genes critical to cell cycle control, genetic stability, and apoptosis have been identified in OS, consensus genetic changes that lead to OS development are poorly understood. Disruption of the osteogenic differentiation pathway may be at least in part responsible for OS tumorigenesis. Current OS management involves chemotherapy and surgery. Peroxisome proliferator-activated receptor (PPAR) agonists and/or retinoids can inhibit OS proliferation and induce apoptosis and may inhibit OS growth by promoting osteoblastic terminal differentiation. Thus, safe and effective PPAR agonists and/or retinoid derivatives can be then used as adjuvant therapeutic drugs for OS therapy. Furthermore, these agents have the potential to be used as chemopreventive agents for the OS patients who undergo the resection of the primary bone tumors in order to prevent local recurrence and/or distal pulmonary metastasis.

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References

Sandberg A, Bridge J . Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet. 2003; 145(1):1-30. View

Seargent J, Yates E, Gill J . GW9662, a potent antagonist of PPARgamma, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARgamma agonist rosiglitazone, independently of PPARgamma activation. Br J Pharmacol. 2004; 143(8):933-7. PMC: 1575954. DOI: 10.1038/sj.bjp.0705973. View

Morrison N, Shine J, Fragonas J, Verkest V, McMenemy M, Eisman J . 1,25-dihydroxyvitamin D-responsive element and glucocorticoid repression in the osteocalcin gene. Science. 1989; 246(4934):1158-61. DOI: 10.1126/science.2588000. View

Takano S, Kubota T, Nishibori H, Hasegawa H, Ishii Y, Nitori N . Pioglitazone, a ligand for peroxisome proliferator-activated receptor-gamma acts as an inhibitor of colon cancer liver metastasis. Anticancer Res. 2009; 28(6A):3593-9. View

Moerman E, Teng K, Lipschitz D, Lecka-Czernik B . Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell. 2004; 3(6):379-89. PMC: 1850101. DOI: 10.1111/j.1474-9728.2004.00127.x. View

Torchia J, Glass C, Rosenfeld M . Co-activators and co-repressors in the integration of transcriptional responses. Curr Opin Cell Biol. 1998; 10(3):373-83. DOI: 10.1016/s0955-0674(98)80014-8. View

Papadaki I, Mylona E, Giannopoulou I, Markaki S, Keramopoulos A, Nakopoulou L . PPARgamma expression in breast cancer: clinical value and correlation with ERbeta. Histopathology. 2005; 46(1):37-42. DOI: 10.1111/j.1365-2559.2005.02056.x. View

Kersten S, Desvergne B, Wahli W . Roles of PPARs in health and disease. Nature. 2000; 405(6785):421-4. DOI: 10.1038/35013000. View

Lemberger T, Desvergne B, Wahli W . Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Annu Rev Cell Dev Biol. 1996; 12:335-63. DOI: 10.1146/annurev.cellbio.12.1.335. View

10.

Thomas D, Johnson S, Sims N, Trivett M, Slavin J, Rubin B . Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma. J Cell Biol. 2004; 167(5):925-34. PMC: 2172443. DOI: 10.1083/jcb.200409187. View

11.

Takeda K, Ichiki T, Tokunou T, Funakoshi Y, Iino N, Hirano K . Peroxisome proliferator-activated receptor gamma activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells. Circulation. 2000; 102(15):1834-9. DOI: 10.1161/01.cir.102.15.1834. View

12.

Filion C, Motoi T, Olshen A, Lae M, Emnett R, Gutmann D . The EWSR1/NR4A3 fusion protein of extraskeletal myxoid chondrosarcoma activates the PPARG nuclear receptor gene. J Pathol. 2008; 217(1):83-93. PMC: 4429309. DOI: 10.1002/path.2445. View

13.

Bren-Mattison Y, Van Putten V, Chan D, Winn R, Geraci M, Nemenoff R . Peroxisome proliferator-activated receptor-gamma (PPAR(gamma)) inhibits tumorigenesis by reversing the undifferentiated phenotype of metastatic non-small-cell lung cancer cells (NSCLC). Oncogene. 2004; 24(8):1412-22. DOI: 10.1038/sj.onc.1208333. View

14.

Rosen E, Spiegelman B . PPARgamma : a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem. 2001; 276(41):37731-4. DOI: 10.1074/jbc.R100034200. View

15.

Sarraf P, Mueller E, Jones D, KING F, DeAngelo D, Partridge J . Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med. 1998; 4(9):1046-52. DOI: 10.1038/2030. View

16.

Abbott B . Review of the expression of peroxisome proliferator-activated receptors alpha (PPAR alpha), beta (PPAR beta), and gamma (PPAR gamma) in rodent and human development. Reprod Toxicol. 2008; 27(3-4):246-257. DOI: 10.1016/j.reprotox.2008.10.001. View

17.

Haydon R, Luu H, He T . Osteosarcoma and osteoblastic differentiation: a new perspective on oncogenesis. Clin Orthop Relat Res. 2006; 454:237-46. DOI: 10.1097/BLO.0b013e31802b683c. View

18.

Ricaud S, Vernus B, Bonnieu A . Response of human rhabdomyosarcoma cell lines to retinoic acid: relationship with induction of differentiation and retinoic acid sensitivity. Exp Cell Res. 2005; 311(2):192-204. DOI: 10.1016/j.yexcr.2005.09.011. View

19.

Wakino S, Kintscher U, Kim S, Yin F, Hsueh W, Law R . Peroxisome proliferator-activated receptor gamma ligands inhibit retinoblastoma phosphorylation and G1--> S transition in vascular smooth muscle cells. J Biol Chem. 2000; 275(29):22435-41. DOI: 10.1074/jbc.M910452199. View

20.

Carpio L, Gladu J, Goltzman D, Rabbani S . Induction of osteoblast differentiation indexes by PTHrP in MG-63 cells involves multiple signaling pathways. Am J Physiol Endocrinol Metab. 2001; 281(3):E489-99. DOI: 10.1152/ajpendo.2001.281.3.E489. View