Autotaxin Expression in Hepatocellular Carcinoma

Memet, Ilker; Tsalkidou, Evanthia; Tsaroucha, Alexandra; Lambropoulou, María; Chatzaki, Εkaterini; Trypsianis, Grigorios; Schizas, Dimitrios; Pitiakoudis, Michail; Simopoulos, Constantinos

doi:10.1080/08941939.2017.1331280

Cited by 13 publications

(14 citation statements)

References 25 publications

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“…Consistent with our finding, Wunsch, et al have demonstrated elevated ATX expression in chronic cholestatic diseases (Wunsch et al, 2016). In addition, a recent study revealed that high ATX expression was detected in hepatocellular carcinoma and was correlated with histological grade and survival rate (Memet et al, 2017). Rather, ATX might be associated with the nature of BA disease itself.…”

Section: Discussionsupporting

confidence: 91%

Peer Review #1 of "Hepatic autotaxin overexpression in infants with biliary atresia (v0.2)"

McGill¹

2018

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Background. Autotaxin (ATX) is a secreted glycoprotein that is involved in the development of hepatic fibrogenesis via the enzymatic production of lysophosphatidic acid. The aim of this study was to investigate hepatic expression of ATX in biliary atresia (BA) compared with non-BA liver controls and to examine the association between ATX expression and clinical outcome in BA. Methods. Liver specimens from BA infants (n=20) were compared with samples from infants who underwent liver biopsy for reasons other than BA (n=14) served as controls. Relative mRNA and protein expression of ATX were quantified using real-time polymerase chain reaction (PCR) and immunohistochemistry. Masson's Trichrome staining was performed to determine the degree of liver fibrosis. Results. Quantitative real-time PCR demonstrated overexpression of ATX mRNA in BA livers. In immunohistochemical evaluation, ATX was positively stained on the hepatic parenchyma and the biliary epithelium in BA patients, as compared to non-BA controls. The immunostaining score of ATX in BA livers was also significantly higher than that observed in non-BA livers (P<0.001). Subgroup analysis revealed that ATX expression in the patients with poor outcome was significantly greater than in those with good outcome (P=0.03). Additionally, there was a positive correlation between hepatic ATX expression and Metavir fibrosis stage in BA livers (r=0.79, P<0.001). Discussion. This study found that mRNA and protein expression of ATX was increased in BA livers. High hepatic ATX expressionat the time of Kasai operation was associated with liver fibrosis and outcome in BA, suggesting that ATX may serve a role as a promising biomarker of the prognosis in biliary atresia.

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Section: Discussionsupporting

confidence: 91%

Peer Review #1 of "Hepatic autotaxin overexpression in infants with biliary atresia (v0.2)"

McGill¹

2018

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“…LPA signaling is magnified and hijacked by cancers (wounds that do not heal) [ 101 ]. Elevated ATX levels have been observed in the blood and malignant tissues from patients with thyroid [ 102 ], lung [ 103 ], breast [ 104 ], liver [ 105 ], pancreatic [ 106 , 107 ], kidney [ 108 ], bladder [ 108 ], and prostate cancer [ 109 ]. As a consequence, LPA levels increase in those cancers [ 107 , 110 , 111 , 112 , 113 ], which has been considered an indicator of poor prognosis [ 110 , 113 ].…”

Section: Upregulation Of Lpa Signaling In Cancersmentioning

confidence: 99%

Lipid Phosphate Phosphatases and Cancer

Tang

Brindley

2020

Biomolecules

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Lipid phosphate phosphatases (LPPs) are a group of three enzymes (LPP1–3) that belong to a phospholipid phosphatase (PLPP) family. The LPPs dephosphorylate a wide spectrum of bioactive lipid phosphates, among which lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P) are two important extracellular signaling molecules. The LPPs are integral membrane proteins, which are localized on plasma membranes and intracellular membranes, including the endoplasmic reticulum and Golgi network. LPPs regulate signaling transduction in cancer cells and demonstrate different effects in cancer progression through the breakdown of extracellular LPA and S1P and other intracellular substrates. This review is intended to summarize an up-to-date understanding about the functions of LPPs in cancers.

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“…Likewise, ATX is overexpressed in multiple human cancer cell lines . It was shown that ATX is associated with the initiation and progression of breast cancer in mice and humans, and that ATX expression in human hepatocellular carcinoma is correlated with tumor grade as well as with the risk of death . Autotaxin quantification by imaging in fibrosis or cancer patients, therefore, has the potential to become an important diagnostic and prognostic tool.…”

Section: Introductionmentioning

confidence: 99%

[¹⁸F]PRIMATX, a New Positron Emission Tomography Tracer for Imaging of Autotaxin in Lung Tissue and Tumor‐Bearing Mice

Briard

Joshi²,

Shanmukhappa³

et al. 2019

ChemMedChem

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Autotaxin (ATX) is a secreted enzyme with tissue levels associated with tissue injury, which increase during wound healing and chronic fibrotic diseases. We selected [18F](R,E)‐3‐(4‐chloro‐2‐((5‐methyl‐2H‐tetrazol‐2‐yl)methyl)phenyl)‐1‐(4‐((5‐(2‐fluoroethoxy)pyridin‐2‐yl)methyl)‐2‐methylpiperazin‐1‐yl)prop‐2‐en‐1‐one ([18F]PRIMATX, [18F]2), a tracer for positron emission tomography, to image ATX expression in vivo. It successfully differentiates expression levels in lung tissue samples from idiopathic pulmonary fibrosis patients, and allows the detection of ATX‐expressing tumors in living mice, confirming its potential for development as a clinical imaging agent.

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Autotaxin Expression in Hepatocellular Carcinoma

Cited by 13 publications

References 25 publications

Peer Review #1 of "Hepatic autotaxin overexpression in infants with biliary atresia (v0.2)"

Peer Review #1 of "Hepatic autotaxin overexpression in infants with biliary atresia (v0.2)"

Lipid Phosphate Phosphatases and Cancer

[¹⁸F]PRIMATX, a New Positron Emission Tomography Tracer for Imaging of Autotaxin in Lung Tissue and Tumor‐Bearing Mice

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Autotaxin Expression in Hepatocellular Carcinoma

Cited by 13 publications

References 25 publications

Peer Review #1 of "Hepatic autotaxin overexpression in infants with biliary atresia (v0.2)"

Peer Review #1 of "Hepatic autotaxin overexpression in infants with biliary atresia (v0.2)"

Lipid Phosphate Phosphatases and Cancer

[18F]PRIMATX, a New Positron Emission Tomography Tracer for Imaging of Autotaxin in Lung Tissue and Tumor‐Bearing Mice

Contact Info

Product

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About

[¹⁸F]PRIMATX, a New Positron Emission Tomography Tracer for Imaging of Autotaxin in Lung Tissue and Tumor‐Bearing Mice