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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4373-4384. Prepublished online as a Blood First Edition Paper on September 4, 2007; DOI 10.1182/blood-2006-07-038026. This Article Full Text (PDF) All Versions of this Article: blood-2006-07-038026v1 110/13/4373    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, L. H. Articles by Farrar, W. L Search for Related Content PubMed PubMed Citation Articles by Wang, L. H. Articles by Farrar, W. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 27, 2006 Accepted July 17, 2007 Inhibition of adhesive interaction between multiple myeloma and bone marrow stromal cells by PPAR crosstalk with NF-B and c/EBP Li Hua Wang*, Xiao Yi Yang, Xiaohu Zhang, and William L Farrar Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD, United States Cancer Stem Cell Section, Laboratory of Cancer Prevention, National Cancer Institute at Frederick, Frederick, MD, United States * Corresponding author; email: lhwang{at}ncifcrf.gov. Binding of multiple myeloma (MM) cells to bone marrow stromal cells (BMSCs) triggers expression of adhesive molecules and secretion of interleukin-6 (IL-6), promoting MM cell growth, survival, drug resistance, and migration, which highlights the possibility of developing and validating novel anti-MM therapeutic strategies targeting MM cells-host BMSC interactions and their sequelae. Recently, we have found that expression of the peroxisome proliferator-activated receptor (PPAR) and its ligands can potently inhibit IL-6-regulated MM cell growth. Here we demonstrate that PPAR agonists 15-d-PGJ2 and troglitazone significantly suppress cell-cell adhesive events, including expression of adhesion molecules and IL-6 secretion from BMSCs triggered by adhesion of MM cells, as well as overcome drug-resistance by a PPAR-dependent mechanism. The synthetic and natural PPAR agonists have diverging and overlapping mechanisms blocking transactivation of transcription factors NF-B and 5'-CCAAT/enhancer binding protein (C/EBP). Both 15-d-PGJ2 and troglitazone blocked C/EBP transcriptional activity by forming PPAR complexes with C/EBP. 15-d-PGJ2 and troglitazone also blocked NF-B activation by recruiting the co-activator PGC-1 from p65/p50 complexes. Additionally, 15-d-PGJ2 had a non-PPAR-dependent effect by inactivation of phosphorylation of IKK and IB. These studies provide the framework for PPAR-based pharmacological strategies targeting adhesive interactions of MM cells with the bone marrow microenvironment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Q. Tian, R. Miyazaki, T. Ichiki, I. Imayama, K. Inanaga, H. Ohtsubo, K. Yano, K. Takeda, and K. Sunagawa Inhibition of Tumor Necrosis Factor-{alpha}-Induced Interleukin-6 Expression by Telmisartan Through Cross-Talk of Peroxisome Proliferator-Activated Receptor-{gamma} With Nuclear Factor {kappa}B and CCAAT/Enhancer-Binding Protein-{beta} Hypertension, May 1, 2009; 53(5): 798 - 804. [Abstract] [Full Text] [PDF] E. L. Schiffrin and P. Paradis Suppression of Peroxisome Proliferator-Activated Receptor-{gamma} Activity by Angiotensin II in Vascular Smooth Muscle Involves Bcr Kinase: The Fire That Drowns The Water Circ. Res., January 2, 2009; 104(1): 4 - 6. [Full Text] [PDF] A. Martinez-Cardus, E. Martinez-Balibrea, E. Bandres, R. Malumbres, A. Gines, J. L. Manzano, M. Taron, J. Garcia-Foncillas, and A. Abad Pharmacogenomic approach for the identification of novel determinants of acquired resistance to oxaliplatin in colorectal cancer Mol. Cancer Ther., January 1, 2009; 8(1): 194 - 202. [Abstract] [Full Text] [PDF] T. M. Garcia-Bates, S. H. Bernstein, and R. P. Phipps Peroxisome Proliferator-Activated Receptor {gamma} Overexpression Suppresses Growth and Induces Apoptosis in Human Multiple Myeloma Cells Clin. Cancer Res., October 15, 2008; 14(20): 6414 - 6425. [Abstract] [Full Text] [PDF] V Costa, D Foti, F Paonessa, E Chiefari, L Palaia, G Brunetti, E Gulletta, A Fusco, and A Brunetti The insulin receptor: a new anticancer target for peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) and thiazolidinedione-PPAR{gamma} agonists Endocr. Relat. Cancer, March 1, 2008; 15(1): 325 - 335. [Abstract] [Full Text] [PDF]

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