The Simultaneous Expression of Peroxisome Proliferator-Activated Receptor Delta and Cyclooxygenase-2 May Enhance Angiogenesis and Tumor Venous Invasion in Tissues of Colorectal Cancers

Yoshinaga, Masahiro; Kitamura, Yosuke; Chaen, Tomohito; Yamashita, Shunsuke; Tsuruta, Satoru; Hisano, Teruaki; Ikeda, Yoichi; Sakai, Hironori; Nakamura, Kazuhiko; Takayanagi, Ryoichi

doi:10.1007/s10620-008-0465-x

Cited by 20 publications

(22 citation statements)

References 32 publications

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“…This finding is consistent with the studies by Takayama and colleagues (8) and Yoshinaga and colleagues (29). The specificity of the PPAR d antibody in the present study was verified by Western blot, which showed a clear band at the expected position of PPAR d protein as shown in Figure 1C.…”

Section: Discussionsupporting

confidence: 94%

Biological Function and Prognostic Significance of Peroxisome Proliferator-Activated Receptor δ in Rectal Cancer

Yang

Zhang

Zhou

et al. 2011

Clinical Cancer Research

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Purpose: To investigate the expression significance of PPAR b/d in relation to radiotherapy (RT), clinicopathologic, and prognostic variables of rectal cancer patients.Experimental Design: We included 141 primary rectal cancer patients who participated in a Swedish clinical trial of preoperative RT. Tissue microarray samples from the excised rectal cancers and the adjacent or distant normal mucosa and lymph node metastases were stained with PPAR d antibody. Survival probability was computed by the Kaplan-Meier method and Cox regression model. The proliferation of colon cancer cell lines KM12C, KM12SM, and KM12L4a was assayed after PPAR d knockdown.Results: PPAR d was increased from adjacent or distant normal mucosa to primary cancers, whereas it decreased from primary cancers to lymph node metastases. After RT, PPAR d was increased in normal mucosa, whereas it decreased in primary cancers and lymph node metastases. In primary cancers, the high expression of PPAR d was related to higher frequency of stage I cases, lower lymph node metastasis rate, and low expression of Ki-67 in the unirradiated cases, and related to favorable survival in the cases either with or without RT. The proliferation of the KM12C, KM12SM, or KM12L4a cells was significantly accelerated after PPAR d knockdown.Conclusions: RT decreases the PPAR d expression in primary rectal cancers and lymph node metastases. PPAR d is related to the early development of rectal cancer and inhibits the proliferation of colorectal cancer cells. Increase of PPAR d predicts favorable survival in the rectal cancer patients either with or without preoperative RT.

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Section: Discussionsupporting

confidence: 94%

Biological Function and Prognostic Significance of Peroxisome Proliferator-Activated Receptor δ in Rectal Cancer

Yang

Zhang

Zhou

et al. 2011

Clinical Cancer Research

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“…The selective PPAR δ agonist GW501516 acts as a tumor promoter in mammary carcinogenesis [19] and colon tumorigenesis [15, 20, 21], whereas disruption of PPAR δ expression blocks mammary [22] and colon tumorigenesis [23, 24]. PPAR δ is regulated by risk factors implicated in cancer progression, including K-Ras [25], Wnt [26], and Pges/Cox2 [22, 27], and is associated with activation of angiogenesis [20, 28–30]. PPAR δ regulates proinflammatory signaling through NF κ B and IL-1 β [31], and is activated by metabolites of arachidonic acid metabolism that serve as PPAR ligands [14, 29, 32].…”

Section: Introductionmentioning

confidence: 99%

Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation

Pollock¹,

Rodriguez²,

Martin

et al. 2010

PPAR Research

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Peroxisome proliferator-activated receptorδ (PPARδ) regulates a multiplicity of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes likely create risk factors associated with the ability of PPARδ agonists to promote tumorigenesis in some organs. In the present study, we describe a new gastric tumor mouse model that is dependent on the potent and highly selective PPARδ agonist GW501516 following carcinogen administration. The progression of gastric tumorigenesis was rapid as determined by magnetic resonance imaging and resulted in highly metastatic squamous cell carcinomas of the forestomach within two months. Tumorigenesis was associated with gene expression signatures indicative of cell adhesion, invasion, inflammation, and metabolism. Increased PPARδ expression in tumors correlated with increased PDK1, Akt, β-catenin, and S100A9 expression. The rapid development of metastatic gastric tumors in this model will be useful for evaluating preventive and therapeutic interventions in this disease.

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“…The proangiogenic properties of PPAR β / δ make this nuclear receptor a new pharmacological target to face ischemic events which may affect heart [69, 70] and brain [71] but also other tissues such as kidney [72]. Regarding tumoral growth, physiological proangiogenic properties of PPAR β / δ might be regarded as undesired properties, potentially strengthening metabolic coupling between tumor and its stroma, and several experimental and clinical reports have incriminated a positive link between PPAR β / δ and tumoral cell growth [73–76]. However, recent evidence highlights that PPAR β / δ and its ligands may also convey, on the opposite, antiangiogenic properties [77, 78].…”

Section: Ppars Inflammation Angiogenesis and Warburg's Effectmentioning

confidence: 99%

PPARs: Interference with Warburg’ Effect and Clinical Anticancer Trials

et al. 2012

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The metabolic/cell signaling basis of Warburg’s effect (“aerobic glycolysis”) and the general metabolic phenotype adopted by cancer cells are first reviewed. Several bypasses are adopted to provide a panoramic integrated view of tumoral metabolism, by attributing a central signaling role to hypoxia-induced factor (HIF-1) in the expression of aerobic glycolysis. The cancer metabolic phenotype also results from alterations of other routes involvingras, myc, p53,andAktsignaling and the propensity of cancer cells to develop signaling aberrances (notably aberrant surface receptor expression) which, when present, offer unique opportunities for therapeutic interventions. The rationale for various emerging strategies for cancer treatment is presented along with mechanisms by which PPAR ligands might interfere directly with tumoral metabolism and promote anticancer activity. Clinical trials using PPAR ligands are reviewed and followed by concluding remarks and perspectives for future studies. A therapeutic need to associate PPAR ligands with other anticancer agents is perhaps an important lesson to be learned from the results of the clinical trials conducted to date.

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The Simultaneous Expression of Peroxisome Proliferator-Activated Receptor Delta and Cyclooxygenase-2 May Enhance Angiogenesis and Tumor Venous Invasion in Tissues of Colorectal Cancers

Cited by 20 publications

References 32 publications

Biological Function and Prognostic Significance of Peroxisome Proliferator-Activated Receptor δ in Rectal Cancer

Biological Function and Prognostic Significance of Peroxisome Proliferator-Activated Receptor δ in Rectal Cancer

Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation

PPARs: Interference with Warburg’ Effect and Clinical Anticancer Trials

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