Exact Criterion for Determining Clustering vs. Reentrant Melting Behavior for Bounded Interaction Potentials

We examine in full generality the phase behavior of systems whose constituent particles interact by means of potentials which do not diverge at the origin, are free of attractive parts and decay fast enough to zero as the interparticle separation r goes to infinity. By employing a mean field-density functional theory which is shown to become exact at high temperatures and/or densities, we establish a criterion which determines whether a given system will freeze at all temperatures or it will display reentrant melting and an upper freezing temperature.Comment: 5 pages, 3 figures, submitted to PRL on March 29, 2000 New version: 10 pages, 9 figures, forwarded to PRE on October 16, 200

Ground state at high density

Weak limits as the density tends to infinity of classical ground states of integrable pair potentials are shown to minimize the mean-field energy functional. By studying the latter we derive global properties of high-density ground state configurations in bounded domains and in infinite space. Our main result is a theorem stating that for interactions having a strictly positive Fourier transform the distribution of particles tends to be uniform as the density increases, while high-density ground states show some pattern if the Fourier transform is partially negative. The latter confirms the conclusion of earlier studies by Vlasov (1945), Kirzhnits and Nepomnyashchii (1971), and Likos et al. (2007). Other results include the proof that there is no Bravais lattice among high-density ground states of interactions whose Fourier transform has a negative part and the potential diverges or has a cusp at zero. We also show that in the ground state configurations of the penetrable sphere model particles are superposed on the sites of a close-packed lattice.Comment: Note adde

Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity

The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2). CLIC3 acts as a glutathione-dependent oxidoreductase that reduces TGM2 and regulates TGM2 binding to its cofactors. Finally, CLIC3 is also secreted by cancer cells, is abundant in the stromal and tumour compartments of aggressive ovarian cancers and its levels correlate with poor clinical outcome. This work reveals a previously undescribed invasive mechanism whereby the secretion of a glutathione-dependent oxidoreductase drives angiogenesis and cancer progression by promoting TGM2-dependent invasion

Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium

Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness‐induced CCN1 activates β‐catenin nuclear translocation and signaling and that this contributes to upregulate N‐cadherin levels on the surface of the endothelium, in vitro. This facilitates N‐cadherin‐dependent cancer cell–endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness‐induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis

Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium

YesTumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro This facilitates N-cadherin-dependent cancer cell-endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness-induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis.Cancer Research UK (CRUK Beatson Institute C596/A17196, CRUK Glasgow Centre C596/A18076 and S.Z. C596/A12935

Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium

Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness‐induced CCN1 activates β‐catenin nuclear translocation and signaling and that this contributes to upregulate N‐cadherin levels on the surface of the endothelium, in vitro. This facilitates N‐cadherin‐dependent cancer cell–endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness‐induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis

Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix

Elevated production of collagen-rich extracellular matrix is a hallmark of cancer-associated fibroblasts (CAFs) and a central driver of cancer aggressiveness. Here we find that proline, a highly abundant amino acid in collagen proteins, is newly synthesized from glutamine in CAFs to make tumour collagen in breast cancer xenografts. PYCR1 is a key enzyme for proline synthesis and highly expressed in the stroma of breast cancer patients and in CAFs. Reducing PYCR1 levels in CAFs is sufficient to reduce tumour collagen production, tumour growth and metastatic spread in vivo and cancer cell proliferation in vitro. Both collagen and glutamine-derived proline synthesis in CAFs are epigenetically upregulated by increased pyruvate dehydrogenase-derived acetyl-CoA levels. PYCR1 is a cancer cell vulnerability and potential target for therapy; therefore, our work provides evidence that targeting PYCR1 may have the additional benefit of halting the production of a pro-tumorigenic extracellular matrix. Our work unveils new roles for CAF metabolism to support pro-tumorigenic collagen production

Chemical potentials and potential distributions of inclusion gas in quenched-annealed random porous media

12 pags., 8 figs., 1 tab.The adsorption of hard-sphere gas in a random porous media and/or in a disordered hard sphere matrix is studied by applying the replica-Ornstein-Zernike (ROZ) equations for the quenched-annealed systems. Our interests are (1) to derive new formulas for the chemical potentials and the potential distributions theorems for such systems and (2) to use these derivations as consistency requirements for improving the closure relations in the ROZ. Two types of consistencies are enforced: (i) bulk thermodynamic property consistencies, such as the Gibbs-Duhem relation and (ii) zero-separation theorems on the cavity functions. Five hard-sphere matrix/hard-sphere fluid systems have been investigated, representing different porosities and size ratios. Direct formulas for the chemical potentials and the zero-separation theorems for the fluid cavity functions are derived and tested. We find uniformly better agreement with Monte Carlo data when self-consistency is enforced, than the conventional closures: such as the Percus-Yevick and hypernetted chain equations. In general, the structural properties are improved, as well as the thermodynamic properties. There remains discrepancy in the fluid-replica structure h 12(r) at coincidence, r = 0. The nature of the h 12(r) behavior is discussed in light of the consistency principles. © 1999 American Institute of Physics.We acknowledge the Spanish Direccion General de Ensenanza Superior e Investigacion Cientıfica for partial support of this project under Grant No. PB97-0258-C02-02 and the sabbatical leave for L.L.L. (Grant No. SAB95-0646

A self-consistent integral equation study of the structure and thermodynamics of the penetrable sphere fluid

7 pags., 11 figs., 2 tabs.The penetrable sphere fluid consists of a system of spherical particles interacting via a potential that remains finite and constant for distances smaller than the particle diameter and is zero otherwise. This system, which was proposed sometime ago as a model for micelles in a solvent, has represented so far a remarkable challenge for integral equation theories which proved unable to correctly model the behavior of the two-body correlations inside the particle overlap region. It is shown in this work that enforcing the fulfillment of zero separation theorems for the cavity distribution function y(r), and thermodynamic consistency conditions (fluctuation vs virial compressibility and Gibbs-Duhem relation), on a parametrized closure of the type proposed by Verlet, leads to an excellent agreement with simulation, both for the thermodynamics and the structure (inside and outside the particle core). Additionally, the behavior of the integral equation at high packing fractions is explored and the bridge functions extracted from simulation are compared with the predictions of the proposed integral equation. © 2000 American Institute of Physics.This work has been supported by the Spanish Direccion General de Ensenanza Superior e Investigacion Cientıfica under Grant No. PB97-0258-C02-02