Additional file 2: of The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer

Figure S2. PDGFR-BB stimulation upregulates CDCP1 in TNBC cells. Western blot analysis of CDCP1 and Vinculin expression in SUM-149 and BT549 cells upon PDGF-BB and ERKi treatment. (PDF 249 kb)

Search for eV (pseudo)scalar penetrating particles in the SPS neutrino beam

We carried out a model-independent search for light scalar or pseudoscalar particles $a$'s (an example of which is the axion) that couple to two photons by using a photon-regeneration method at high energies allowing a substantial increase in the sensitivity to $eV$ masses.\ The experimental set-up is based on elements of the CERN West Area Neutrino Facility (WANF) beam line and theNOMAD neutrino detector.\ The new particles, if they exist, could be produced through the Primakoff effect in interactions of high energy photons, generated by the 450 $GeV$ protons in the CERN SPS neutrino target, with virtual photons from the WANF horn magnetic field.\ The particles would penetrate the downstre…

A novel CXCR4 antagonist counteracts paradoxical generation of cisplatin-induced pro-metastatic niches in lung cancer.

Platinum-based chemotherapy remains widely used in advanced non-small cell lung cancer (NSCLC) despite experimental evidence of its potential to induce long-term detrimental effects, including the promotion of pro-metastatic microenvironments. In this study, we investigated the interconnected pathways underlying the promotion of cisplatin-induced metastases. In tumor-free mice, cisplatin treatment resulted in an expansion in the bone marrow of CCR2+CXCR4+Ly6Chigh inflammatory monocytes (IMs) and an increase in lung levels of stromal SDF-1, the CXCR4 ligand. In experimental lung metastasis assays, cisplatin-induced IMs promoted the extravasation of tumor cells and the expansion of CD133+CXCR…

Circulating mir-320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk

miRNAs play a central role in the complex signaling network of cancer cells with the tumor microenvironment. Little is known on the origin of circulating miRNAs and their relationship with the tumor microenvironment in lung cancer. Here, we focused on the cellular source and relative contribution of different cell types to circulating miRNAs composing our risk classifier of lung cancer using in vitro/in vivo models and clinical samples. A cell‐type specific expression pattern and topography of several miRNAs such as mir‐145 in fibroblasts, mir‐126 in endothelial cells, mir‐133a in skeletal muscle cells was observed in normal and lung cancer tissues. Granulocytes and platelets are the major …

Inclusive production of ρ0(770), f0(980) and f2(1270) mesons in νμ charged current interactions

The inclusive production of the meson resonances $\rho^{0}(770)$, $f_0(980)$ and $f_2(1270)$ in neutrino-nucleus charged current interactions has been studied with the NOMAD detector exposed to the wide band neutrino beam generated by 450 GeV protons at the CERN SPS. For the first time the $f_{0}(980)$ meson is observed in neutrino interactions. The statistical significance of its observation is 6 standard deviations. The presence of $f_{2}(1270)$ in neutrino interactions is reliably established. The average multiplicity of these three resonances is measured as a function of several kinematic variables. The experimental results are compared to the multiplicities obtained from a simulation b…

Additional file 1: of The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer

Figure S1. Gating strategy for CDCP1 flow cytometric analysis. Flow cytometric analysis of MDA-MB-231 cells starved in serum-free medium for 24 h and then treated for 48 h with FGF 50 ng/mL. (PDF 470 kb)

The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer

Background CDCP1, a transmembrane protein with tumor pro-metastatic activity, was recently identified as a prognostic marker in TNBC, the most aggressive breast cancer subtype still lacking an effective molecular targeted therapy. The mechanisms driving CDCP1 over-expression are not fully understood, although several stimuli derived from tumor microenvironment, such as factors present in Wound Healing Fluids (WHFs), reportedly increase CDCP1 levels. Methods The expression of CDCP1, PDGFRβ and ERK1/2cell was tested by Western blot after stimulation of MDA-MB-231 cells with PDGF-BB and, similarly, in presence or not of ERK1/2 inhibitor in a panel of TNBC cell lines. Knock-down of PDGFRβ was e…

P2.01-017 Circulating miRNAs in Lung Cancer Are Associated to Pro-Tumorigenic and Immunosuppressive Microenvironment

Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: A nested case-control study

We evaluated the aberrant promoter methylation profile of a panel of 3 genes in DNA from tumor and sputum samples, in view of a complementary approach to spiral computed tomography (CT) for early diagnosis of lung cancer. The aberrant promoter methylation of RARbeta2, p16(INK4A) and RASSF1A genes was evaluated by methylation-specific PCR in tumor samples of 29 CT-detected lung cancer patients, of which 18 had tumor-sputum pairs available for the analysis, and in the sputum samples from 112 cancer-free heavy smokers enrolled in a spiral CT trial. In tumor samples from 29 spiral CT-detected patients, promoter hypermethylation was identified in 19/29 (65.5%) cases for RARbeta2, 12/29 (41.4%) f…

Abstract 4981: Circulating mir-320 promotes immunosuppressive macrophages M2 phenotype associated with lung cancer progression

Abstract INTRODUCTION miRNAs play a role in the complex network of signaling between cancer cells and tumor microenvironment. We previously reported the identification of diagnostic miRNA signatures (MSC) based on 24-miRNAs in plasma samples of lung cancer patients detected by low dose computed tomography (LDCT) screening. MATERIAL and METHODS To evaluate the potential origin of the miRNAs of the diagnostic signature, we analyzed their expression by real-time or digital PCR in both cells and conditioned medium (CM) from different cell types of the lung microenvironment as well as in plasma samples of heavy smokers and patients. Lung tissues and cell-blocks were analyzed by miRNAs in situ hy…

SDF-1/CXCR4 inhibition prevents paradoxical generation of cisplatin-induced pro-metastatic niches

AbstractPlatinum-based chemotherapy remains widely used in advanced non-small cell lung cancer (NSCLC) despite its ineffectiveness in long-term control of metastasis.Here, we uncover the interconnected pathways subtending cisplatin-induced metastasis promotion.We report that cisplatin treatment of tumor-free mice results in bone-marrow expansion of CCR2+CXCR4+Ly6Chigh inflammatory monocytes (IM) concomitantly with increased levels in the lungs of stromal SDF-1, the CXCR4 ligand. In experimental metastasis assays, cisplatin-induced IM favor tumor cells extravasation and expansion of CD133+CXCR4+ metastasis initiating cells (MICs), facilitating lung metastasis formation. At the primary tumor,…

Genomic Profiling of Patient-Derived Xenografts for Lung Cancer Identifies B2M Inactivation Impairing Immunorecognition

Abstract Purpose: We aimed to maximize the performance of detecting genetic alterations in lung cancer using high-throughput sequencing for patient-derived xenografts (PDXs). Experimental Design: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of β2-microglobulin (B2M), a component of the HLA class-I complex. Results: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance. We extended the mutational analysis of B2M to about 230 lung cancers. Five percent of the lung cancers carried somatic mutations, most of which impaired the correct formation of the HLA-I complex. …

Antibody–Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non–small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade

Abstract Purpose: Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified. Experimental Design: Among 187 patients with non–small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell–deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutat…