PPAR Research

Retracted: Rosiglitazone Suppresses the Growth and Invasiveness of SGC-7901 Gastric Cancer Cells and Angiogenesis In Vitro via PPAR<i>&#x03B3;</i> Dependent and Independent Mechanisms

Dipak Panigrahy

Arja Kaipainen

Mark W. Kieran

Sui Huang

PPARs: A Double-Edged Sword in Cancer Therapy?

Lung cancer is the leading cause of cancer death in the United States and five-year survival remains low. Numerous studies have shown that chronic inflammation may lead to progression of carcinogenesis. As a result of inflammatory stimulation, arachidonic acid (AA) metabolism produces proliferation mediators through complex and dynamic interactions of the products of the LOX/COX enzymes. One important mediator in the activation of the AA pathways is the nuclear protein PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M2" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg>. Targeting LOX/COX enzymes and inducing activation of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M3" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> have resulted in significant reduction of cell growth in lung cancer cell lines. However, specific COX-inhibitors have been correlated with an increased cardiovascular risk. Clinical applications are still being explored with a novel generation of dual LOX/COX inhibitors. PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M4" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> activation through synthetic ligands (TZDs) has revealed a great mechanistic complexity since effects are produced through PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M5" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg>-dependent and -independent mechanisms. Furthermore, PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M6" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> could also be involved in regulation of COX-2. Overexpression of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M7" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> has reported to play a role in control of invasion and differentiation. Exploring the function of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M8" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg>, in this new context, may provide a better mechanistic model of its role in cancer and give an opportunity to design a more efficient therapeutic approach in combination with LOX/COX inhibitors.

Jordi Tauler

James L. Mulshine

Combination Therapy of PPAR<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z" /></g></svg> Ligands and Inhibitors of Arachidonic Acid in Lung Cancer

In this review, the role of NF-<svg     style="vertical-align:-0.1638pt;width:8.7375002px;" id="M3" height="7.9499998" version="1.1" viewBox="0 0 8.7375002 7.9499998" width="8.7375002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D705"/></g>

		
	
</svg>B in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF-<svg     style="vertical-align:-0.1638pt;width:8.7375002px;" id="M4" height="7.9499998" version="1.1" viewBox="0 0 8.7375002 7.9499998" width="8.7375002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D705"/></g>

		
	
</svg>B in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor-<svg     style="vertical-align:-0.1638pt;width:9.7749996px;" id="M5" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg> (PPAR<svg     style="vertical-align:-0.1638pt;width:9.7749996px;" id="M6" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg>) activation in non-hepatic tissues can lead to the inhibition of NF-<svg     style="vertical-align:-0.1638pt;width:8.7375002px;" id="M7" height="7.9499998" version="1.1" viewBox="0 0 8.7375002 7.9499998" width="8.7375002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D705"/></g>

		
	
</svg>B activation. Several lines of evidence support the hypothesis that the activation of NF-<svg     style="vertical-align:-0.1638pt;width:8.7375002px;" id="M8" height="7.9499998" version="1.1" viewBox="0 0 8.7375002 7.9499998" width="8.7375002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D705"/></g>

		
	
</svg>B by peroxisome proliferators in the liver is mediated by oxidative stress. The role of NF-<svg     style="vertical-align:-0.1638pt;width:8.7375002px;" id="M9" height="7.9499998" version="1.1" viewBox="0 0 8.7375002 7.9499998" width="8.7375002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D705"/></g>

		
	
</svg>B in peroxisome proliferator-induced hepatocarcinogenesis has been examined using NF-<svg     style="vertical-align:-0.1638pt;width:8.7375002px;" id="M10" height="7.9499998" version="1.1" viewBox="0 0 8.7375002 7.9499998" width="8.7375002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg>B knockout models. Specifically, the induction of cell proliferation and the promotion of liver carcinogenesis are inhibited in mice lacking the p50 subunit of NF-<svg     style="vertical-align:-0.1638pt;width:8.7375002px;" id="M11" height="7.9499998" version="1.1" viewBox="0 0 8.7375002 7.9499998" width="8.7375002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D705"/></g>

		
	
</svg>B. Overall, the activation of NF-<svg     style="vertical-align:-0.1638pt;width:8.7375002px;" id="M12" height="7.9499998" version="1.1" viewBox="0 0 8.7375002 7.9499998" width="8.7375002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg>B appears to be important in the carcinogenic activity of peroxisome proliferators.

Howard P. Glauert

Karen Calfee-Mason

Yixin Li

Vani Nilakantan

Michelle L. Twaroski

Job Tharappel

Brett T. Spear

The Role of NF-<svg style="vertical-align:-0.1638pt" height="7.9499998" version="1.1" viewBox="0 0 8.7375002 7.9499998" width="8.7375002" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D705" d="M484 406q0 -21 -22 -38q-10 -7 -18 -1q-15 11 -30 11q-30 0 -77.5 -37t-74.5 -67l79 -168q11 -23 19.5 -34.5t13 -14t10.5 -2.5q9 0 30 17.5t40 42.5l17 -23q-31 -45 -57.5 -69.5t-40.5 -29.5t-31 -5q-18 0 -32 13.5t-35 55.5q-34 71 -69 160q-36 -32 -59 -56&#xA;q-12 -27 -36 -158q-44 -7 -77 -15l-5 7l82 349q6 25 -2 25q-16 0 -72 -41l-14 22q44 41 89 69.5t66 28.5q19 0 19 -32q0 -16 -6 -43l-35 -160l146 143q94 92 136 92q20 0 33 -12t13 -30z" /></g></svg>B in PPAR<svg style="vertical-align:-0.1638pt" height="7.9499998" version="1.1" viewBox="0 0 9.7749996 7.9499998" width="9.7749996" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FC" d="M545 106q-67 -118 -134 -118q-24 0 -40 37.5t-30 129.5h-2q-47 -72 -103 -119.5t-108 -47.5q-47 0 -76 45.5t-29 119.5q0 113 85 204t174 91q47 0 70 -33.5t43 -119.5h3q32 47 80 140l55 13l10 -9q-47 -80 -138 -201q17 -99 27.5 -136t22.5 -37q23 0 69 61zM333 204&#xA;q-14 98 -31 149.5t-50 51.5q-49 0 -94 -70t-45 -164q0 -55 15.5 -86t40.5 -31q70 0 164 150z" /></g></svg>-Mediated Hepatocarcinogenesis

Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B<sub  >4</sub> receptor pathway and the PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M3" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed as a potent leukotriene B<sub  >4</sub> receptor antagonist for treatment of inflammatory conditions. LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. LY293111 was shown to have potent anticancer effects in pancreatic cancer and several other solid malignancies, where it caused cell cycle arrest and marked apoptosis. Subsequently, it came to light that LY293111 exhibited PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M4" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> agonist activity in addition to its effects on the 5-lipoxygenase pathway. This raises the question of which of the two targets is of greatest importance with regard to the anticancer effects of this agent. The evidence to date is not conclusive, but suggests that the effects of LY293111 may be mediated by both <svg style="vertical-align:-3.13504pt;width:34.799999px;" id="M5" height="14.375" version="1.1" viewBox="0 0 34.799999 14.375" width="34.799999"  xmlns="http://www.w3.org/2000/svg">
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</svg> receptors and PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M6" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg>.

Thomas E. Adrian

Rene Hennig

Helmut Friess

Xianzhong Ding

The Role of PPAR<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z" /></g></svg> Receptors and Leukotriene <svg style="vertical-align:-3.27605pt" height="15.25" version="1.1" viewBox="0 0 16.450001 15.25" width="16.450001" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x42" d="M372 352v-2q176 -27 176 -159q0 -99 -95 -151q-73 -40 -196 -40h-221v28q65 5 78.5 19t13.5 76v404q0 63 -12 77t-72 18v28h257q102 0 150 -34q26 -18 41 -48.5t15 -65.5q0 -111 -135 -150zM213 362h47q80 0 117.5 32t37.5 96q0 56 -33 92t-100 36q-41 0 -56 -10&#xA;q-13 -8 -13 -50v-196zM213 328v-203q0 -54 17 -72.5t66 -18.5q67 1 110.5 37t43.5 110q0 147 -192 147h-45z" /></g><g transform="matrix(.012,-0,0,-.012,10.062,15.187)"><path id="x34" d="M456 178h-96v-72q0 -51 12.5 -62.5t72.5 -16.5v-27h-256v27q65 5 78 17t13 62v72h-260v28q182 271 300 426h40v-407h96v-47zM280 225v295h-2q-107 -148 -196 -295h198z" /></g></svg> Receptors in Mediating the Effects of LY293111 in Pancreatic Cancer

Lipid mediators can trigger physiological responses by activating nuclear hormone receptors, such as the peroxisome proliferator-activated receptors (PPARs). PPARs, in turn, control the expression of networks of genes encoding proteins involved in all aspects of lipid metabolism. In addition, PPARs are tumor growth modifiers, via the regulation of cancer cell apoptosis, proliferation, and differentiation, and through their action on the tumor cell environment, namely, angiogenesis, inflammation, and immune cell functions. Epidemiological studies have established that tumor progression may be exacerbated by chronic inflammation. Here, we describe the production of the lipids that act as activators of PPARs, and we review the roles of these receptors in inflammation and cancer. Finally, we consider emerging strategies for therapeutic intervention.

Liliane Michalik

Walter Wahli

PPARs Mediate Lipid Signaling in Inflammation and Cancer

The role of PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M2" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg> in adipocyte differentiation has fueled intense interest in the function of this steroid nuclear receptor for regulation of malignant cell growth and differentiation. Given the antiproliferative and differentiating effects of PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M3" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg> ligands on liposarcoma cells, investigation of PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M4" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg> expression and ligand activation in other solid tumors such as breast, colon, and prostate cancers ensued.  The anticancer effects of PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M5" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg> ligands in cell culture and rodent models of a multitude of tumor types suggest broad applicability of these agents to cancer therapy.  This review focuses on the clinical use of PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M6" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg> ligands, specifically the thiazolidinediones, for the treatment and prevention of cancer.

Jennifer L. Hatton

Lisa D. Yee

Clinical Use of PPAR<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z"/></g></svg> Ligands in Cancer

Peroxisome proliferator-activated receptor gamma (PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M2" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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	</g>
</svg>) is a ligand-activated transcription factor, which belongs to the family of nuclear hormone receptors. Recent in vitro studies have shown that PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M3" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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			</text>

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</svg> can regulate the transcription of <i>phosphatase and tensin homolog on chromosome </i><i  >ten</i> (<i  >PTEN</i>), a known tumor suppressor. <i  >PTEN</i> is a susceptibility gene for a number of disorders, including breast and thyroid cancer. Activation of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M4" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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</svg> through agonists increases functional PTEN protein levels that subsequently induces apoptosis and inhibits cellular growth, which suggests that PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M5" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> may be a tumor suppressor. Indeed, several in vivo studies have demonstrated that genetic alterations of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M6" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> can promote tumor progression. These results are supported by observations of the beneficial effects of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M7" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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</svg> agonists in the in vivo cancer setting. These studies signify the importance of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M8" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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</svg> and <i  >PTEN</i>&#x27;s interaction in cancer prevention.

Rosemary E. Teresi

Kristin A. Waite

PPAR<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z" /></g></svg>, PTEN, and the Fight against Cancer

The growth and metastasis of cancers intimately involve the vasculature and in particular the endothelial cell layer. Tumours require new blood vessel formation via angiogenesis to support growth. In addition, inflammation, coagulation, and platelet activation are common signals in the growth and metastasis of tumour cells. The endothelium plays a central role in the homeostatic control of inflammatory cell recruitment, regulating platelet activation and coagulation pathways. PPAR<svg style="vertical-align:-0.1254pt;width:8.9375px;" id="M1" height="7.1750002" version="1.1" viewBox="0 0 8.9375 7.1750002" width="8.9375"  xmlns="http://www.w3.org/2000/svg">
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</svg>, -<svg style="vertical-align:-2.29482pt;width:8.8500004px;" id="M2" height="13.425" version="1.1" viewBox="0 0 8.8500004 13.425" width="8.8500004"  xmlns="http://www.w3.org/2000/svg">
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			<text transform="matrix(1,0,0,-1,-71.95,63.6)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛽</tspan>
			</text>

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	</g>
</svg>/<svg style="vertical-align:-0.13794pt;width:7.9875002px;" id="M3" height="10.7375" version="1.1" viewBox="0 0 7.9875002 10.7375" width="7.9875002"  xmlns="http://www.w3.org/2000/svg">
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			<text transform="matrix(1,0,0,-1,-71.95,63.6)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛿</tspan>
			</text>

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</svg>, and -<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M4" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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</svg> are all expressed in endothelial cells. This review will discuss the roles of PPARs in endothelial cells in relation to angiogenesis, inflammation, coagulation, and platelet control pathways. In particular, we will discuss the recent evidence that supports the hypothesis that PPAR<svg style="vertical-align:-0.1254pt;width:8.9375px;" id="M5" height="7.1750002" version="1.1" viewBox="0 0 8.9375 7.1750002" width="8.9375"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,7.175)">
		<g transform="translate(72,-66.26)">
			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛼</tspan>
			</text>

		</g>
	</g>
</svg> and PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M6" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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</svg> are antiangiogenic receptors, while PPAR<svg style="vertical-align:-2.29482pt;width:8.8500004px;" id="M7" height="13.425" version="1.1" viewBox="0 0 8.8500004 13.425" width="8.8500004"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,13.425)">
		<g transform="translate(72,-61.26)">
			<text transform="matrix(1,0,0,-1,-71.95,63.6)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛽</tspan>
			</text>

		</g>
	</g>
</svg>/<svg style="vertical-align:-0.13794pt;width:7.9875002px;" id="M8" height="10.7375" version="1.1" viewBox="0 0 7.9875002 10.7375" width="7.9875002"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,10.7375)">
		<g transform="translate(72,-63.41)">
			<text transform="matrix(1,0,0,-1,-71.95,63.6)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛿</tspan>
			</text>

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	</g>
</svg> is proangiogenic.

David Bishop-Bailey

Karen E. Swales

The Role of PPARs in the Endothelium: Implications  for Cancer Therapy

PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M2" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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	</g>
</svg> is a member of the ligand-activated nuclear receptor superfamily: its ligands act as insulin sensitizers and some are approved for the treatment of metabolic disorders in humans. PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M3" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

		</g>
	</g>
</svg> has pleiotropic effects on survival and proliferation of multiple cell types, including cancer cells, and is now subject of intensive preclinical cancer research. Studies of the recent decade highlighted PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M4" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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	</g>
</svg> role as a potential modulator of angiogenesis in vitro and in vivo. These observations provide an additional facet to the PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M5" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

		</g>
	</g>
</svg> image as potential anticancer drug. Currently PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M6" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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</svg> is regarded as an important target for the therapies against angiogenesis-dependent pathological states including cancer and vascular complications of diabetes. Some of the studies, however, identify pro-angiogenic and tumor-promoting effects of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M7" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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	</g>
</svg> and its ligands pointing out the need for further studies. Below, we summarize current knowledge of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M8" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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	</g>
</svg> regulatory mechanisms and molecular targets, and discuss ways to maximize the beneficial activity of the PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M9" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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	</g>
</svg> agonists.

Dorina Veliceasa

Frank Thilo Schulze-Ho&#235;pfner

Olga V. Volpert

PPAR<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z" /></g></svg> and Agonists against Cancer: Rational Design of Complementation Treatments

About this journal

<p><em>PPAR Research</em> publishes articles related to mechanisms involved in the activation of peroxisome proliferator-activated receptors, as well as their role in regulation of cellular differentiation, development, energy homeostasis and metabolic function.</p>


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<p>Chief Editor, Dr Xiao-Jie Lu, is dedicated to basic and translational research on liver diseases. His research at Nanjing Medical University, China, focuses&nbsp;on exploring these diseases' underlying mechanisms that may be translatable to novel diagnostic biomarkers or therapeutic targets.</p>


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PPAR Research publishes articles related to mechanisms involved in the activation of peroxisome proliferator-activated receptors, as well as their role in regulation of cellular differentiation, development, energy homeostasis and metabolic function.

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PPAR Research

PPARs: A Double-Edged Sword in Cancer Therapy?

PPARs: A Double-Edged Sword in Cancer Therapy?

Articles

Retracted: Rosiglitazone Suppresses the Growth and Invasiveness of SGC-7901 Gastric Cancer Cells and Angiogenesis In Vitro via PPARγ Dependent and Independent Mechanisms

PPARs: A Double-Edged Sword in Cancer Therapy?

Combination Therapy of PPAR Ligands and Inhibitors of Arachidonic Acid in Lung Cancer

The Role of NF-B in PPAR-Mediated Hepatocarcinogenesis

The Role of PPAR Receptors and Leukotriene Receptors in Mediating the Effects of LY293111 in Pancreatic Cancer

PPARs Mediate Lipid Signaling in Inflammation and Cancer

Clinical Use of PPAR Ligands in Cancer

PPAR, PTEN, and the Fight against Cancer

The Role of PPARs in the Endothelium: Implications for Cancer Therapy

PPAR and Agonists against Cancer: Rational Design of Complementation Treatments