Epithelial-to-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma and Pancreatic Tumor Cell Lines: The Role of Neutrophils and Neutrophil-Derived Elastase

Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with fibrosis and a prominent inflammatory infiltrate in the desmoplastic stroma. Moreover, in PDAC, an epithelial-to-mesenchymal transition (EMT) is observed. To explore a possible connection between the infiltrating cells, particularly the polymorphonuclear neutrophils (PMN) and the tumor cell transition, biopsies of patients with PDAC (n=115) were analysed with regard to PMN infiltration and nuclear expression of β-catenin and of ZEB1, well-established indicators of EMT. In biopsies with a dense PMN infiltrate, a nuclear accumulation of β-catenin and of ZEB1 was observed. To address the question whether PMN could induce EMT, they were isolated from healthy donors and were cocultivated with pancreatic tumor cells grown as monolayers. Rapid dyshesion of the tumor cells was seen, most likely due to an elastase-mediated degradation of E-cadherin. In parallel, the transcription factor TWIST was upregulated, β-catenin translocated into the nucleus, ZEB1 appeared in the nucleus, and keratins were downregulated. EMT was also induced when the tumor cells were grown under conditions preventing attachment to the culture plates. Here, also in the absence of elastase, E-cadherin was downmodulated. PMN as well as prevention of adhesion induced EMT also in liver cancer cell line. In conclusion, PMN via elastase induce EMT in vitro, most likely due to the loss of cell-to-cell contact. Because in pancreatic cancers the transition to a mesenchymal phenotype coincides with the PMN infiltrate, a contribution of the inflammatory response to the induction of EMT and—by implication—to tumor progression is possible

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Jet-hadron correlations measured relative to the second order event plane in Pb–Pb collisions at √sNN = 2.76 TeV

The Quark Gluon Plasma (QGP) produced in ultra relativistic heavy-ion collisions at the Large Hadron Collider (LHC) can be studied by measuring the modifications of jets formed by hard scattered partons which interact with the medium. We studied these modifications via angular correlations of jets with charged hadrons for jets with momenta 20 < pjetT < 40 GeV/c as a function of the associated particle momentum. The reaction plane fit (RPF) method is used in this analysis to remove the flow modulated background. The analysis of angular correlations for different orientations of the jet relative to the second order event plane allows for the study of the path length dependence of medium modifications to jets. We present the dependence of azimuthal angular correlations of charged hadrons with respect to the angle of the axis of a reconstructed jet relative to the event plane in Pb-Pb collisions at sNN−−−√ = 2.76 TeV. The dependence of particle yields associated with jets on the angle of the jet with respect to the event plane is presented. Correlations at different angles relative to the event plane are compared through ratios and differences of the yield. No dependence of the results on the angle of the jet with respect to the event plane is observed within uncertainties, which is consistent with no significant path length dependence of the medium modifications for this observable

Production of (anti-)3He and (anti-)3H in p–Pb collisions at √sNN = 5.02 TeV

The transverse momentum (pT) differential yields of (anti-)3He and (anti-)3H measured in p-Pb collisions at sNN−−−√ = 5.02 TeV with ALICE at the LHC are presented. The ratios of the pT-integrated yields of (anti-)3He and (anti-)3H to the proton yields are reported, as well as the pT dependence of the coalescence parameters B3 for (anti-)3He and (anti-)3H. For (anti-)3He, the results obtained in four classes of the mean charged-particle multiplicity density are also discussed. These results are compared to predictions from a canonical statistical hadronization model and coalescence approaches. An upper limit on the total yield of 4He¯ is determined

J/ψ elliptic and triangular flow in Pb–Pb collisions at √sNN = 5.02 TeV

The inclusive J/ψ elliptic (v2) and triangular (v3) flow coefficients measured at forward rapidity (2.5 <y< 4) and the v2 measured at midrapidity (|y|< 0.9) in Pb-Pb collisions at sNN−−−√ = 5.02 TeV using the ALICE detector at the LHC are reported. The entire Pb-Pb data sample collected during Run 2 is employed, amounting to an integrated luminosity of 750 μb−1 at forward rapidity and 93 μb−1 at midrapidity. The results are obtained using the scalar product method and are reported as a function of transverse momentum pT and collision centrality. At midrapidity, the J/ψ v2 is in agreement with the forward rapidity measurement. The centrality averaged results indicate a positive J/ψ v3 with a significance of more than 5σ at forward rapidity in the pT range 2<pT<5 GeV/c. The forward rapidity v2, v3, and v3/v2 results at low and intermediate pT (pT≲8 GeV/c) exhibit a mass hierarchy when compared to pions and D mesons, while converging into a species-independent curve at higher pT. At low and intermediate pT, the results could be interpreted in terms of a later thermalization of charm quarks compared to light quarks, while at high pT, path-length dependent effects seem to dominate. The J/ψ v2 measurements are further compared to a microscopic transport model calculation. Using a simplified extension of the quark scaling approach involving both light and charm quark flow components, it is shown that the D-meson vn measurements can be described based on those for charged pions and J/ψ flow

Production of muons from heavy−flavour hadron decays at high transverse momentum in Pb−Pb collisions at √sNN = 5.02 and 2.76 TeV

Measurements of the production of muons from heavy-flavour hadron decays in Pb−Pb collisions at sNN−−−√ = 5.02 and 2.76 TeV using the ALICE detector at the LHC are reported. The nuclear modification factor RAA at sNN−−−√ = 5.02 TeV is measured at forward rapidity (2.5<y<4) as a function of transverse momentum pT in central, semi-central, and peripheral collisions over a wide pT interval, 3<pT<20 GeV/c, in which a significant contribution of muons from beauty-hadron decays is expected at high pT. With a significantly improved precision compared to the measurements at lower collision energy, the RAA shows an increase of the suppression of the yields of muons from heavy-flavour hadron decays with increasing centrality. A suppression by a factor of about three is observed in the 10% most central collisions. The RAA at sNN−−−√ = 5.02 is similar to that reported at 2.76 TeV in a broader pT interval and with an improved accuracy with respect to previously published measurements. The precise RAA results have the potential to distinguish between model predictions implementing different mechanisms of parton energy loss in the high-density medium formed in heavy-ion collisions. The results place stringent constraints on the relative energy loss between charm and beauty quarks

Elliptic and triangular flow of (anti)deuterons in Pb–Pb collisions at √sNN = 5.02 TeV

The measurements of the (anti)deuterons elliptic flow (v2) and the first measurements of triangular flow (v3) in Pb-Pb collisions at a center-of-mass energy per nucleon-nucleon collisions sNN−−−√ = 5.02 TeV are presented. A mass ordering at low transverse momentum (pT) is observed when comparing these measurements with those of other identified hadrons, as expected from relativistic hydrodynamics. The measured (anti)deuterons v2 lies between the predictions from the simple coalescence and blast-wave models, which provide a good description of the data only for more peripheral and for more central collisions, respectively. The mass number scaling, which is violated for v2, is approximately valid for the (anti)deuterons v3. The measured v2 and v3 are also compared with the predictions from a coalescence approach with phase-space distributions of nucleons generated by iEBE-VISHNU with AMPT initial conditions coupled with UrQMD, and from a dynamical model based on relativistic hydrodynamics coupled to the hadronic afterburner SMASH. The model predictions are consistent with the data within the uncertainties in mid-central collisions, while a deviation is observed in central centrality intervals

Measurement of spin-orbital angular momentum interactions in relativistic heavy-ion collisions

The first measurement of spin alignment of vector mesons (K∗0 and ϕ) in heavy-ion collisions at the Large Hadron Collider (LHC) is reported. The measurements are carried out as a function of transverse momentum (pT ) and collision centrality with the ALICE detector using the particles produced at midrapidity (|y|< 0.5) in Pb-Pb collisions at a center-of-mass energy (sNN−−−√) of 2.76 TeV. The second diagonal spin density matrix element (ρ00 ) is measured from the angular distribution of the decay daughters of the vector meson in the decay rest frame, with respect to the normal of both the event plane and the production plane. The ρ00 values are found to be less than 1/3 (= 1/3 implies no spin alignment) at low pT (< 2 GeV/c) for both vector mesons. The observed deviations from 1/3 are maximal for mid-central collisions at a level of 3σ for K∗0 and 2σ for ϕ mesons. As control measurements, the analysis is also performed using the K0S meson, which has zero spin, and for the vector mesons in pp collisions; in both cases no significant spin alignment is observed. The ρ00 values at low pT with respect to the production plane are closer to 1/3 than for the event plane; they are related to each other through correlations introduced by the elliptic flow in the system. The measured spin alignment is surprisingly large compared to the polarization measured for Λ hyperons, but qualitatively consistent with the expectation from models which attribute the spin alignment to a polarization of quarks in the presence of large initial angular momentum in non-central heavy-ion collisions and a subsequent hadronization by the process of recombination

ΛK femtoscopy in Pb–Pb collisions at √sNN = 2.76 TeV

The first measurements of the scattering parameters of ΛK pairs in all three charge combinations (ΛK+, ΛK−, and ΛK0S) are presented. The results are achieved through a femtoscopic analysis of ΛK correlations in Pb-Pb collisions at sNN−−−√ = 2.76 TeV recorded by ALICE at the LHC. The femtoscopic correlations result from strong final-state interactions, and are fit with a parametrization allowing for both the characterization of the pair emission source and the measurement of the scattering parameters for the particle pairs. Extensive studies with the THERMINATOR 2 event generator provide a good description of the non-femtoscopic background, which results mainly from collective effects, with unprecedented precision. Furthermore, together with HIJING simulations, this model is used to account for contributions from residual correlations induced by feed-down from particle decays. The extracted scattering parameters indicate that the strong force is repulsive in the ΛK+ interaction and attractive in the ΛK− interaction. The data hint that the and ΛK0S interaction is attractive, however the uncertainty of the result does not permit such a decisive conclusion. The results suggest an effect arising either from different quark-antiquark interactions between the pairs (ss¯ in ΛK+ and uu¯¯¯ in ΛK−) or from different net strangeness for each system (S = 0 for ΛK+, and S = −2 for ΛK−). Finally, the ΛK systems exhibit source radii larger than expected from extrapolation from identical particle femtoscopic studies. This effect is interpreted as resulting from the separation in space-time of the single-particle Λ and K source distributions