Hsp60 Is Actively Secreted by Human Tumor Cells

Background: Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. Methodology/Principal Findings: Since cancer cells may undergo necrosis and apoptosis, it could be possible that extracellular Hsps are chiefly the result of cell destruction but not the product of an active, physiological process. In this work, we studied three tumor cells lines and found that they all release Hsp60 into the culture media by an active mechanism independently of cell death. Biochemical analyses of one of the cell lines revealed that Hsp60 secretion was significantly reduced, by inhibitors of exosomes and lipid rafts. Conclusions/Significance: Our data suggest that Hsp60 release is the result of an active secretion mechanism and, since extracellular release of the chaperone was demonstrated in all tumor cell lines investigated, our observations most likel

Hsp20 Functions as a Novel Cardiokine in Promoting Angiogenesis via Activation of VEGFR2

Heat shock proteins (Hsps) are well appreciated as intrinsic protectors of cardiomyocytes against numerous stresses. Recent studies have indicated that Hsp20 (HspB6), a small heat shock protein, was increased in blood from cardiomyopathic hamsters. However, the exact source of the increased circulating Hsp20 and its potential role remain obscure. In this study, we observed that the circulating Hsp20 was increased in a transgenic mouse model with cardiac-specific overexpression of Hsp20, compared with wild-type mice, suggesting its origin from cardiomyocytes. Consistently, culture media harvested from Hsp20-overexpressing cardiomyocytes by Ad.Hsp20 infection contained an increased amount of Hsp20, compared to control media. Furthermore, we identified that Hsp20 was secreted through exosomes, independent of the endoplasmic reticulum-Golgi pathway. To investigate whether extracellular Hsp20 promotes angiogenesis, we treated human umbilical vein endothelial cells (HUVECs) with recombinant human Hsp20 protein, and observed that Hsp20 dose-dependently promoted HUVEC proliferation, migration and tube formation. Moreover, a protein binding assay and immunostaining revealed an interaction between Hsp20 and VEGFR2. Accordingly, stimulatory effects of Hsp20 on HUVECs were blocked by a VEGFR2 neutralizing antibody and CBO-P11 (a VEGFR inhibitor). These in vitro data are consistent with the in vivo findings that capillary density was significantly enhanced in Hsp20-overexpressing hearts, compared to non-transgenic hearts. Collectively, our findings demonstrate that Hsp20 serves as a novel cardiokine in regulating myocardial angiogenesis through activation of the VEGFR signaling cascade

Observation of the diphoton decay of the Higgs boson and measurement of its properties

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Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

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Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

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Search for quark compositeness in dijet angular distributions from pp collisions at √s̅ = 7 TeV

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Search for supersymmetry in hadronic final states using MT2 in pp collisions at √s = 7 TeV

Open Access: This article is distributed under the terms of the Creative Commons Attribution License.-- et al.A search for supersymmetry or other new physics resulting in similar final states is presented using a data sample of 4.73 fb−1 of pp collisions collected at √s = 7 TeV with the CMS detector at the LHC. Fully hadronic final states are selected based on the variable M T2, an extension of the transverse mass in events with two invisible particles. Two complementary studies are performed. The first targets the region of parameter space with medium to high squark and gluino masses, in which the signal can be separated from the standard model backgrounds by a tight requirement on M T2. The second is optimized to be sensitive to events with a light gluino and heavy squarks. In this case, the M T2 requirement is relaxed, but a higher jet multiplicity and at least one b-tagged jet are required. No significant excess of events over the standard model expectations is observed. Exclusion limits are derived for the parameter space of the constrained minimal supersymmetric extension of the standard model, as well as on a variety of simplified model spectra.European Commission; Federal Ministry of Science, Research and Economy (Austria); Agency for Innovation by Science and Technology (Belgium); Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil); Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro; Fundação de Amparo à Pesquisa do Estado de São Paulo; Colciencias (Colombia); Ministry of Science, Education and Sports of the Republic of Croatia; Research Promotion Foundation (Cyprus); Centre National de la Recherche Scientifique (France); Bundesministerium für Bildung und Forschung (Deutschland); Deutsche Forschungsgemeinschaft; General Secretariat of Research and Technology (Greece); National Office for Research and Technology (Hungary); Institute for Research in Fundamental Sciences (Iran); Science Foundation Ireland; Istituto Nazionale di Fisica Nucleare (Italia); National Research Foundation of Korea; Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (México); Consejo Nacional de Ciencia y Tecnología (México); Secretaría de Educación Pública (México); Universidad Autónoma de San Luis Potosí; Pakistan Atomic Energy Commission; Fundação para a Ciência e a Tecnologia (Portugal); Joint Institute for Nuclear Research (Russia); Russian Foundation for Basic Research; Ministry of Education, Science and Technological Development (Serbia); Ministerio de Ciencia e Innovación (España); Centro Nacional de Física de Partículas, Astropartículas y Nuclear (España); Swiss National Science Foundation; The Scientific and Technological Research Council of Turkey; Turkish Atomic Energy Authority; Alfred P. Sloan Foundation; Alexander von Humboldt Foundation; Science and Technology Facilities Council (UK); Department of Energy (US); National Science Foundation (US).Peer Reviewe

Measurement of Higgs boson production and properties in the WW decay channel with leptonic final states

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Search for supersymmetry in events with b jets and missing transverse momentum at the LHC

A search for supersymmetry is presented using a sample of events with b jets and missing transverse momentum. The search uses a data sample of proton-proton collisions at a centre-of-mass energy of 7TeV, corresponding to an integrated luminosity of 35 pb(-1), collected with the CMS detector. A total of 0.33(-0.33)(+0.43) (stat.) +/- 0.13 (syst.) events is predicted, using control samples in the data, to arise from standard model processes, and one event is observed in the data. Upper limits are set at the 95% confidence level on the cross sections of benchmark supersymmetric models

Search for the pair production of light top squarks in the e(+/-)mu(-/+) final state in proton-proton collisions at root s=13 TeV

A search for the production of a pair of top squarks at the LHC is presented. This search targets a region of parameter space where the kinematics of top squark pair production and top quark pair production are very similar, because of the mass difference between the top squark and the neutralino being close to the top quark mass. The search is performed with 35.9 fb(-1) of proton-proton collisions at a centre-of-mass energy of root s = 13 TeV, collected by the CMS detector in 2016, using events containing one electron-muon pair with opposite charge. The search is based on a precise estimate of the top quark pair background, and the use of the M-T2 variable, which combines the transverse mass of each lepton and the missing transverse momentum. No excess of events is found over the standard model predictions. Exclusion limits are placed at 95% confidence level on the production of top squarks up to masses of 208 GeV for models with a mass difference between the top squark and the lightest neutralino close to that of the top quark.Peer reviewe