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Author Keshamouni, Venkateshwar G. ♦ Arenberg, Douglas A. ♦ Reddy, Raju C. ♦ Newstead, Michael J. ♦ Anthwal, Shalini ♦ St, Theodore J.
Source CiteSeerX
Content type Text
File Format PDF
Subject Domain (in DDC) Computer science, information & general works ♦ Data processing & computer science
Subject Keyword Ppar-g Activation Inhibits Angiogenesis ♦ Elr Cxc Chemokine Production ♦ Non-small Cell Lung Cancer1 ♦ A549 Cell ♦ Nf-kb Activation ♦ Primary Tumor Growth ♦ Peroxisome Proliferator ♦ Factor Viii Antibody ♦ Con-ditioned Medium ♦ Tumor-associated Angiogenesis ♦ Transam Reporter Gene ♦ Pio-treated Tumor ♦ Immunohistochemical Analysis ♦ Active Ppar ♦ Tro-treated A549 Cell ♦ Cxcl1 Production ♦ Blood Vessel Density ♦ Vp16 Ppar ♦ Hmvec Chemotaxis ♦ Antiangiogenic Effect Likely Contribute ♦ Nf-kb Transcriptional Activity ♦ Angiogenic Elr Cxc ♦ Various Type ♦ Untreated A549 Cell ♦ Significant Reduction ♦ Tumor-bearing Scid Mouse ♦ Transient Transfection ♦ Recent Study ♦ Elr Cxc Chemokines ♦ Control Animal ♦ Nf-kb Dependent Regulation ♦ Human Microvascular Endothelial Cell ♦ Tumor Growth ♦ Induces Growth Arrest
Abstract Activation of peroxisome proliferator–activated receptor-; (PPAR-;) results in inhibition of tumor growth in various types of cancers, but the mecha-nism(s) by which PPAR-; induces growth arrest has not been completely defined. In a recent study, we demonstrated that treatment of A549 (human non small cell lung cancer cell line) tumor-bearing SCID mice with PPAR-; ligands troglitazone (Tro) and pioglitazone significantly inhibits primary tumor growth. In this study, immunohistochemical analysis of Tro-treated and Pio-treated tumors with factor VIII antibody revealed a significant reduction in blood vessel density compared to tumors in control animals, suggesting inhibition of angiogenesis. Further analysis showed that treatment of A549 cells in vitro with Tro or transient transfection of A549 cells with constitutively active PPAR-; (VP16–PPAR-;) construct blocked the pro-duction of the angiogenic ELR +CXC chemokines IL-8 (CXCL8), ENA-78 (CXCL5), and Gro-A (CXCL1). Simi-larly, an inhibitor of NF-KB activation (PDTC) also blocked CXCL8, CXCL5, and CXCL1 production, con-sistent with their NF-KB–dependent regulation. Con-ditioned media from A549 cells induce human microvascular endothelial cell (HMVEC) chemotaxis. However, conditioned media from Tro-treated A549 cells induced significantly less HMVEC chemotaxis compared to untreated A549 cells. Furthermore, PPAR-; activation inhibited NF-KB transcriptional activity, as assessed by TransAM reporter gene assay. Collectively, our data suggest that PPAR-; ligands can inhibit tumor-associated angiogenesis by blocking the production of ELR+CXC chemokines, which is mediated through antagonizing NF-KB activation. These antiangiogenic effects likely contribute to the inhibition of primary tumor growth by PPAR-; ligands.
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Research
Education Level UG and PG ♦ Career/Technical Study