Macrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies.

Extensive transcriptional and ontogenetic diversity exists among normal tissue-resident macrophages, with unique transcriptional profiles endowing the cells with tissue-specific functions. However, it is unknown whether the origins of different macrophage populations affect their roles in malignancy. Given potential artifacts associated with irradiation-based lineage tracing, it remains unclear if bone-marrow-derived macrophages (BMDMs) are present in tumors of the brain, a tissue with no homeostatic involvement of BMDMs. Here, we employed multiple models of murine brain malignancy and genetic lineage tracing to demonstrate that BMDMs are abundant in primary and metastatic brain tumors. Our data indicate that distinct transcriptional networks in brain-resident microglia and recruited BMDMs are associated with tumor-mediated education yet are also influenced by chromatin landscapes established before tumor initiation. Furthermore, we demonstrate that microglia specifically repress Itga4 (CD49D), enabling its utility as a discriminatory marker between microglia and BMDMs in primary and metastatic disease in mouse and human

Inactivation of Brettanomyces bruxellensis by High Hydrostatic Pressure technology

Póster presentado en el XXV Congreso de la Sociedad Española de Microbiología (SEM), celebrado en Logroño del 7 al 10 de julio de 2015.Peer Reviewe

Pleiotropic functions of the tumor- and metastasis-suppressing Matrix Metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity which has onco-suppressive actions in numerous tumor types

Overexpression of Cathepsin Z Contributes to Tumor Metastasis by Inducing Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

The aim of this study was to characterize the oncogenic function and mechanism of Cathepsin Z (CTSZ) at 20q13.3, a frequently amplified region in hepatocellular carcinoma (HCC). Real-time PCR were used to compare CTSZ expression between paired HCC tumor and non-tumor specimens. CTSZ gene was stably transfected into HCC line QGY-7703 cells and its role in tumorigenicity and cell motility was characterized by soft agar, wound-healing, transwell invasion and cell adhesion assay, and tumor xenograft mouse model. Western blot analysis was used to study expression of proteins associated with epithelial-mesenchymal transition (EMT)

Synaptic proximity enables NMDAR signalling to promote brain metastasis.

Metastasis-the disseminated growth of tumours in distant organs-underlies cancer mortality. Breast-to-brain metastasis (B2BM) is a common and disruptive form of cancer and is prevalent in the aggressive basal-like subtype, but is also found at varying frequencies in all cancer subtypes. Previous studies revealed parameters of breast cancer metastasis to the brain, but its preference for this site remains an enigma. Here we show that B2BM cells co-opt a neuronal signalling pathway that was recently implicated in invasive tumour growth, involving activation by glutamate ligands of N-methyl-D-aspartate receptors (NMDARs), which is key in model systems for metastatic colonization of the brain and is associated with poor prognosis. Whereas NMDAR activation is autocrine in some primary tumour types, human and mouse B2BM cells express receptors but secrete insufficient glutamate to induce signalling, which is instead achieved by the formation of pseudo-tripartite synapses between cancer cells and glutamatergic neurons, presenting a rationale for brain metastasis.This work was principally supported by grants from the Swiss National Science Foundation and the European Research Council, and by a gift from the Biltema Foundation that was administered by the ISREC Foundation, Lausanne, Switzerland

Preclinical Models of Brain Metastasis

Research at the Brain Metastasis Group is supported by MINECO grants MINECO-Retos SAF2017-89643-R (M.V.), Bristol-Myers Squibb- Melanoma Research Alliance Young Investigator Award 2017 (498103) (M.V.), Beug Foundation’s Prize for Metastasis Research 2017 (M.V.), Fundación Ramón Areces (CIVP19S8163) (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972)N

Phenotypic characterisation of regulatory T cells in dogs reveals signature transcripts conserved in humans and mice

Regulatory T cells (Tregs) are a double-edged regulator of the immune system. Aberrations of Tregs correlate with pathogenesis of inflammatory, autoimmune and neoplastic disorders. Phenotypically and functionally distinct subsets of Tregs have been identified in humans and mice on the basis of their extensive portfolios of monoclonal antibodies (mAb) against Treg surface antigens. As an important veterinary species, dogs are increasingly recognised as an excellent model for many human diseases. However, insightful study of canine Tregs has been restrained by the limited availability of mAb. We therefore set out to characterise CD4+CD25high T cells isolated ex vivo from healthy dogs and showed that they possess a regulatory phenotype, function, and transcriptomic signature that resembles those of human and murine Tregs. By launching a cross-species comparison, we unveiled a conserved transcriptomic signature of Tregs and identified that transcript hip1 may have implications in Treg function

Inactivation of Brettanomyces bruxellensis by High Hydrostatic Pressure technology

© 2015. High Hydrostatic Pressure (HHP) technology was tested on two strains of Brettanomyces bruxellensis isolated from Rioja red wines for analyzing the microbial inactivation reached in different oenological conditions. With this purpose, these strains were inoculated in synthetic wine with different pH and ethanol content. The inactivations reached with 100MPa, 200MPa and 300MPa applied from one to seven minutes were tested just after the treatment and after a week.Current consumers demand quality, free-additive wines. This has made oenological industry search alternative non-thermal technologies. The present results supported that high pH and high ethanol wines shortly treated at 100MPa made B.bruxellensis undetectable. Moreover, low pH and low ethanol wines content should be at least treated at 200MPa, and wines with intermediate ethanol content should be carefully analyzed in terms of strain composition before applying HHP. Finally, treatments at 300MPa managed a complete inactivation regardless of oenological conditions.This work has been supported by funding and pre-doctoral grant (B.O.E. 12th May, 2012) of the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria project RTA2011-00070-00-00 and FEDER of the European Community.Peer Reviewe

Inactivation of Brettanomyces bruxellensis by High Hydrostatic Pressure technology

High Hydrostatic Pressure (HHP) technology was tested on two strains of Brettanomyces bruxellensis isolated from Rioja red wines for analyzing the microbial inactivation reached in different oenological conditions. With this purpose, these strains were inoculated in synthetic wine with different pH and ethanol content. The inactivations reached with 100MPa, 200MPa and 300MPa applied from one to seven minutes were tested just after the treatment and after a week.Current consumers demand quality, free-additive wines. This has made oenological industry search alternative non-thermal technologies. The present results supported that high pH and high ethanol wines shortly treated at 100MPa made B.bruxellensis undetectable. Moreover, low pH and low ethanol wines content should be at least treated at 200MPa, and wines with intermediate ethanol content should be carefully analyzed in terms of strain composition before applying HHP. Finally, treatments at 300MPa managed a complete inactivation regardless of oenological conditions. © 2015