Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis

Henry, Laurent; Lavabre‐Bertrand, Thierry; Vercambre, Lucille; Ramos, Jason; Carillo, Serge; Guiraud, Isabelle; Pouderoux, Philippe; Bismuth, Michaël; Jc, Valats; Dematteï, Chritophe; Duny, Yohan; Chaze, I.; Funakoshi, Natalie; Jp, Bureau; Jp, Daurès; Blanc, Peggy

doi:10.1136/gut.2008.157016

Cited by 38 publications

(29 citation statements)

References 29 publications

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“…The results for healthy subjects are, in general, consistent with those obtained by other investigators, who, using ELISA-based assay have demonstrated that the average concentrations of plasma 20S proteasome in the controls are between 2100 and 2600 ng·mL-1 [17–19, 21]. However, it should be mentioned that other groups of investigators have demonstrated that 20S proteasome antigen concentration in plasma or serum from normal subjects was less than 400 ng·mL-1 [16, 20, 40].…”

Section: Resultssupporting

confidence: 90%

SPR imaging biosensor for the 20S proteasome: sensor development and application to measurement of proteasomes in human blood plasma

2011

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The 20S proteasome is a multicatalytic enzyme complex responsible for intracellular protein degradation in mammalian cells. Its antigen level or enzymatic activity in blood plasma are potentially useful markers for various malignant and nonmalignant diseases. We have developed a method for highly selective determination of the 20S proteasome using a Surface Plasmon Resonance Imaging (SPRI) technique. It is based on the highly selective interaction between the proteasome’s catalytic β5 subunit and immobilized inhibitors (the synthetic peptide PSI and epoxomicin). Inhibitor concentration and pH were optimized. Analytical responses, linear ranges, accuracy, precision and interferences were investigated. Biosensors based on either PSI and epoxomicin were found to be suitable for quantitative determination of the proteasome, with a precision of ±10% for each, and recoveries of 102% and 113%, respectively, and with little interference by albumin, trypsin, chymotrypsin, cathepsin B and papain. The proteasome also was determined in plasma of healthy subjects and of patients suffering from acute leukemia. Both biosensors gave comparable results (2860 ng·mL-1 on average for control, and 42300 ng·mL-1 on average for leukemia patients).FigureThe synthetic peptide aldehyde Z-Ile-Glu(OBut)-Ala-Leu-H (PSI) and a microbial α’,β’ epoxyketone peptide epoxomicin was used to develop SPRI biosensor for the highly selective determination of the 20S proteasome concentration, and to evaluate the sensor applicability for the determination of 20S proteasome in human blood plasma.

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Section: Resultssupporting

confidence: 90%

SPR imaging biosensor for the 20S proteasome: sensor development and application to measurement of proteasomes in human blood plasma

2011

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“…So far, circulating proteasome has been detected in patients with solid tumors using the ELISA test employing antibodies directed against the constitutive α subunits of the 20S proteasome [25][26][27][28][29][30]. However, ELISA-based assay Fig.…”

Section: Discussionmentioning

confidence: 99%

Increased plasma proteasome chymotrypsin-like activity in patients with advanced solid tumors

et al. 2011

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The chymotrypsin-like (ChT-L) activity is one of the key regulators of intracellular protein degradation. Elevated proteasome ChT-L activity has recently been reported in plasma of patients with leukemia and myelodysplastic syndrome and suggested to have a prognostic significance. The aim of the present study was to evaluate plasma proteasome ChT-L activity in patients with newly diagnosed solid tumors at early and advanced stages of the disease. The activity was assayed using the fluorogenic peptide substrate, Suc-Leu-Leu-Val-Tyr-AMC, in a cohort of 155 patients with early/advanced rectal (n=43/29), gastric (n=6/13), and breast (n=37/27) cancer and compared with that in normal individuals (n=55). The median plasma proteasome ChT-L activity was elevated by 20-32% in patients with advanced stage of rectal, gastric, and breast cancer compared with healthy donors. The difference turned out to be statistically significant (P<0.001). By contrast, values in patients with early stage of malignancies were not significantly different from those observed in normal individuals. We also found that plasma proteasome activity correlated with serum carcinoembryonic antigen levels in the group of patients with rectal cancer (r=0.433, P<0.05). Elevated plasma proteasome ChT-L activity is indicative of advanced stage of rectal, gastric, and breast cancer. However, the activity does not seem to be a parameter with clinically relevant potential in terms of early detection of cancer in this subset of patients.

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“…Extracellular proteasome has been proposed as a suitable biomarker in some cancers and autoimmune diseases, potentially allowing for better diagnosis, patient stratification, and prediction of the response to therapy18192021, even though its function is not yet understood. Here, we elucidate one of its potential functions in the extracellular space.…”

Section: Discussionmentioning

confidence: 99%

“…microparticle/ectosomes shedding from the surface of T lymphocytes16, or exosomes derived from endocytic compartments of mesenchymal stem cells17. In patients with solid tumors and hematological malignancies, extracellular proteasome levels increase and correlate with occurrence, severity, as well as clinical outcome of the diseases181920. In some autoimmune diseases, such as rheumatoid arthritis, MS and systemic lupus erythematosus, extracellular proteasome levels are increased and are markers of cell damage and immunological activity2122.…”

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confidence: 99%

Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis

Dianzani

Bellavista

Liepe

et al. 2017

Sci Rep

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Osteopontin is a pleiotropic cytokine that is involved in several diseases including multiple sclerosis. Secreted osteopontin is cleaved by few known proteases, modulating its pro-inflammatory activities. Here we show by in vitro experiments that secreted osteopontin can be processed by extracellular proteasomes, thereby producing fragments with novel chemotactic activity. Furthermore, osteopontin reduces the release of proteasomes in the extracellular space. The latter phenomenon seems to occur in vivo in multiple sclerosis, where it reflects the remission/relapse alternation. The extracellular proteasome-mediated inflammatory pathway may represent a general mechanism to control inflammation in inflammatory diseases.

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Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis

Abstract: The plasma proteasome level is a reliable marker of malignant transformation in patients with cirrhosis, even when there is a low tumour mass.

Cited by 38 publications

References 29 publications

SPR imaging biosensor for the 20S proteasome: sensor development and application to measurement of proteasomes in human blood plasma

SPR imaging biosensor for the 20S proteasome: sensor development and application to measurement of proteasomes in human blood plasma

Increased plasma proteasome chymotrypsin-like activity in patients with advanced solid tumors

Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis

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