Dataset Information

Peroxisome Proliferator-Activated Receptor ? Expression Is Inversely Associated with Macroscopic Vascular Invasion in Human Hepatocellular Carcinoma.

ABSTRACT: Peroxisome proliferator-activated receptor ? (PPAR?) is a ligand-activated nuclear receptor that regulates cellular lipid and glucose metabolism and also plays an inhibitory role in various cancers. However, the role of PPAR? in hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the prognostic value of PPAR? in HCC and its role in inhibiting tumor progression, namely, HCC cell growth, migration, and angiogenesis. Immunohistochemical PPAR? staining was examined in 83 HCC specimens to investigate the clinicopathological correlations between PPAR? expression and various parameters. The functional role of PPAR? was determined via PPAR? overexpression and knockdown in HCC cells. Patients with low HCC tissue PPAR? expression were significantly younger (p = 0.006), and exhibited more tumor numbers (p = 0.038), more macroscopic vascular invasion (MVI) (p = 0.008), and more advanced TNM (size of primary tumor, number of regional lymph nodes, and distant metastasis) stages at diagnosis (p = 0.013) than patients with high HCC tissue PPAR? expression. PPAR? knockdown increased HCC cell growth, migration, and angiogenesis, while PPAR? overexpression reduced HCC cell growth, migration, and angiogenesis. These results suggest that low PPAR? expression is an independent predictor of more MVI in HCC patients. PPAR? contributes to the suppression of HCC cell growth, migration, and angiogenesis. Therefore, PPAR? may be a therapeutic target in HCC patients.

SUBMITTER: Hsu HT

PROVIDER: S-EPMC5000624 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Peroxisome Proliferator-Activated Receptor γ Expression Is Inversely Associated with Macroscopic Vascular Invasion in Human Hepatocellular Carcinoma.

Hsu Hui-Tzu HT Sung Ming-Ta MT Lee Chih-Chun CC Kuo Yin-Ju YJ Chi Chin-Wen CW Lee Hsin-Chen HC Hsia Cheng-Yuan CY

International journal of molecular sciences 20160729 8

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor that regulates cellular lipid and glucose metabolism and also plays an inhibitory role in various cancers. However, the role of PPARγ in hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the prognostic value of PPARγ in HCC and its role in inhibiting tumor progression, namely, HCC cell growth, migration, and angiogenesis. Immunohistochemical PPARγ staining was examined ...[more]

PMID: 27483249

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Project description:Peroxisome proliferator-activated receptor-? (PPAR?) plays an important role in the vasculature; however, the role of PPAR? in abdominal aortic aneurysms (AAA) is not well understood. We hypothesized that PPAR? in smooth muscle cells (SMCs) attenuates the development of AAA. We also investigated PPAR?-mediated signaling pathways that may prevent the development of AAA.We determined whether periaortic application of CaCl(2) renders vascular SMC-selective PPAR? knockout (SMPG KO) mice more susceptible to destruction of normal aortic wall architecture.There is evidence of increased vessel dilatation in the abdominal aorta 6 weeks after 0.25M periaortic CaCl(2) application in SMPG KO mice compared with littermate controls (1.4 ± 0.3 mm [n = 8] vs 1.1 ± 0.2 mm [n = 7]; P = .000119). Results from SMPG KO mice indicate medial layer elastin degradation was greater 6 weeks after abluminal application of CaCl(2) to the abdominal aorta (P < .01). Activated cathepsin S, a potent elastin-degrading enzyme, was increased in SMPG KO mice vs wild-type controls. To further identify a role of PPAR? signaling in reducing the development of AAA, we demonstrated that adenoviral-mediated PPAR? overexpression in cultured rat aortic SMCs decreases (P = .022) the messenger RNA levels of cathepsin S. In addition, a chromatin immunoprecipitation assay detected PPAR? bound to a peroxisome proliferator-activated receptor response element (PPRE) -141 to -159 bp upstream of the cathepsin S gene sequence in mouse aortic SMCs. Also, adenoviral-mediated PPAR? overexpression and knockdown in cultured rat aortic SMCs decreases (P = .013) and increases (P = .018) expression of activated cathepsin S. Finally, immunohistochemistry demonstrated a greater inflammatory infiltrate in SMPG KO mouse aortas, as evidenced by elevations in F4/80 and tumor necrosis factor-? expression.In this study, we identify PPAR? as an important contributor in attenuating the development of aortic aneurysms by demonstrating that loss of PPAR? in vascular SMCs promotes aortic dilatation and elastin degradation. Thus, PPAR? activation may be potentially promising medical therapy in reducing the risk of AAA progression and rupture.

Dataset Information

Peroxisome Proliferator-Activated Receptor ? Expression Is Inversely Associated with Macroscopic Vascular Invasion in Human Hepatocellular Carcinoma.

Publications

Peroxisome Proliferator-Activated Receptor γ Expression Is Inversely Associated with Macroscopic Vascular Invasion in Human Hepatocellular Carcinoma.

Similar Datasets

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