NOX4-dependent ROS production by stromal mammary cells modulates epithelial MCF-7 cell migration

BACKGROUND: The influence of the stromal microenvironment on the progression of epithelial cancers has been demonstrated. Unravelling the mechanisms by which stromal cells affect epithelial behaviour will contribute in understanding cellular malignancy. It has been proposed that redox environment has a role in the acquisition of malignancy. In this work, we studied the influence of epithelial cells on the stromal redox status and the consequence of this phenomenon on MCF-7 cell motility. METHODS: We analysed in a co-culture system, the effect of RMF-EG mammary stromal cells on the migratory capacity of MCF-7 cell line. To test whether the NOX-dependent stromal redox environment influences the epithelial migratory behaviour, we knocked down the expression of NOX4 using siRNA strategy. The effect of TGF-b1 on NOX4 expression and activity was analysed by qPCR, and intracellular ROS production was measured by a fluorescent method. RESULTS: Migration of MCF-7 breast epithelial cells was stimulated when co-cultured with RMF-EG cells. This effect depends on stromal NOX4 expression that, in turn, is enhanced by epithelial soluble factors. Pre-treatment of stromal cells with TGF-b1 enhanced this migratory stimulus by elevating NOX4 expression and intracellular ROS production. TGF-b1 seems to be a major component of the epithelial soluble factors that stimulate NOX4 expression. CONCLUSIONS: Our results have identified that an increased stromal oxidative status, mainly provided by an elevated NOX4 expression, is a permissive element in the acquisition of epithelial migratory properties. The capacity of stromal cells to modify their intracellular ROS production, and accordingly, to increase epithelial motility, seems to depend on epithelial soluble factors among which TGF-b1 have a decisive role.This work was supported by the grant (1080196 to JM) from the Fondo Nacional de Ciencia y Tecnologı´a (FONDECYT) of Chile

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum

Multiplexed Quantum Dot Labeling of Activated c-Met Signaling in Castration-Resistant Human Prostate Cancer

The potential application of multiplexed quantum dot labeling (MQDL) for cancer detection and prognosis and monitoring therapeutic responses has attracted the interests of bioengineers, pathologists and cancer biologists. Many published studies claim that MQDL is effective for cancer biomarker detection and useful in cancer diagnosis and prognosis, these studies have not been standardized against quantitative biochemical and molecular determinations. In the present study, we used a molecularly characterized human prostate cancer cell model exhibiting activated c-Met signaling with epithelial to mesenchymal transition (EMT) and lethal metastatic progression to bone and soft tissues as the gold standard, and compared the c-Met cell signaling network in this model, in clinical human prostate cancer tissue specimens and in a castration-resistant human prostate cancer xenograft model. We observed c-Met signaling network activation, manifested by increased phosphorylated c-Met in all three. The downstream survival signaling network was mediated by NF-κB and Mcl-1 and EMT was driven by receptor activator of NF-κB ligand (RANKL), at the single cell level in clinical prostate cancer specimens and the xenograft model. Results were confirmed by real-time RT-PCR and western blots in a human prostate cancer cell model. MQDL is a powerful tool for assessing biomarker expression and it offers molecular insights into cancer progression at both the cell and tissue level with high degree of sensitivity

A Review of One-Way and Two-Way Experiments to Test the Isotropy of the Speed of Light

As we approach the 125th anniversary of the Michelson-Morley experiment in 2012, we review experiments that test the isotropy of the speed of light. Previous measurements are categorized into one-way (single-trip) and two-way (round-trip averaged or over closed paths) approaches and the level of experimental verification that these experiments provide is discussed. The isotropy of the speed of light is one of the postulates of the Special Theory of Relativity (STR) and, consequently, this phenomenon has been subject to considerable experimental scrutiny. Here, we tabulate significant experiments performed since 1881 and attempt to indicate a direction for future investigation.Comment: Updated Fig. 7 and references; Revised sections 3.2 and 4. Accepted in the Indian Journal of Physics on March 30, 201

Mycorrhizal fungi enhance plant nutrient acquisition and modulate nitrogen loss with variable water regimes

Climate change will alter both the amount and pattern of precipitation and soil water availability, which will directly affect plant growth and nutrient acquisition, and potentially, ecosystem functions like nutrient cycling and losses as well. Given their role in facilitating plant nutrient acquisition and water stress resistance, arbuscular mycorrhizal (AM) fungi may modulate the effects of changing water availability on plants and ecosystem functions. The well-characterized mycorrhizal tomato (Solanum lycopersicum L.) genotype 76R (referred to as MYC+) and the mutant mycorrhiza-defective tomato genotype rmc were grown in microcosms in a glasshouse experiment manipulating both the pattern and amount of water supply in unsterilized field soil. Following 4 weeks of differing water regimes, we tested how AM fungi affected plant productivity and nutrient acquisition, short-term interception of a 15NH4+ pulse, and inorganic nitrogen (N) leaching from microcosms. AM fungi enhanced plant nutrient acquisition with both lower and more variable water availability, for instance increasing plant P uptake more with a pulsed water supply compared to a regular supply and increasing shoot N concentration more when lower water amounts were applied. Although uptake of the short-term 15NH4+ pulse was higher in rmc plants, possibly due to higher N demand, AM fungi subtly modulated NO3- leaching, decreasing losses by 54% at low and high water levels in the regular water regime, with small absolute amounts of NO3- leached (<1 kg N/ha). Since this study shows that AM fungi will likely be an important moderator of plant and ecosystem responses to adverse effects of more variable precipitation, management strategies that bolster AM fungal communities may in turn create systems that are more resilient to these changes.Timothy M. Bowles, Louise E. Jackson, Timothy R. Cavagnar