Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model.

Background: Presence of nerves in tumours, by axonogenesis and neurogenesis, is gaining increased attention for its impact on cancer initiation and development, and the new field of cancer neuroscience is emerging. A recent study in prostate cancer suggested that the tumour microenvironment may influence cancer progression by recruitment of Doublecortin (DCX)-expressing neural progenitor cells (NPCs). However, the presence of such cells in human breast tumours has not been comprehensively explored.

Development of 42 marker panel for in-depth study of cancer associated fibroblast niches in breast cancer using imaging mass cytometry.

Imaging Mass Cytometry (IMC) is a novel, and formidable high multiplexing imaging method emerging as a promising tool for in-depth studying of tissue architecture and intercellular communications. Several studies have reported various IMC antibody panels mainly focused on studying the immunological landscape of the tumor microenvironment (TME). With this paper, we wanted to address cancer associated fibroblasts (CAFs), a component of the TME very often underrepresented and not emphasized enough in present IMC studies.

Hypoxia induced responses are reflected in the stromal proteome of breast cancer.

Cancers are often associated with hypoxia and metabolic reprogramming, resulting in enhanced tumor progression. Here, we aim to study breast cancer hypoxia responses, focusing on secreted proteins from low-grade (luminal-like) and high-grade (basal-like) cell lines before and after hypoxia. We examine the overlap between proteomics data from secretome analysis and laser microdissected human breast cancer stroma, and we identify a 33-protein stromal-based hypoxia profile (33P) capturing differences between luminal-like and basal-like tumors.

Vessel size as a marker of survival in estrogen receptor positive breast cancer.

Purpose: Angiogenesis is crucial for tumor growth and is one of the hallmarks of cancer. In this study, we analyzed microvessel density, vessel median size, and perivascular a-SMA expression as prognostic biomarkers in breast cancer.

Methods: Dual IHC staining was performed where alpha-SMA antibodies were used together with antibodies against the endothelial cell marker CD34.

Global and single-cell proteomics view of the co-evolution between neural progenitors and breast cancer cells in a co-culture model.

Tumor neurogenesis, a process by which new nerves invade tumors, is a growing area of interest in cancer research. Nerve presence has been linked to aggressive features of various solid tumors, including breast and prostate cancer. A recent study suggested that the tumor microenvironment may influence cancer progression through recruitment of neural progenitor cells from the central nervous system.

GADL1 is a multifunctional decarboxylase with tissue-specific roles in β-alanine and carnosine production.

Carnosine and related β-alanine-containing peptides are believed to be important antioxidants, pH buffers, and neuromodulators. However, their biosynthetic routes and therapeutic potential are still being debated. This study describes the first animal model lacking the enzyme glutamic acid decarboxylase-like 1 (GADL1).

Structure of the mouse acidic amino acid decarboxylase GADL1.

Pyridoxal 5'-phosphate (PLP) is a ubiquitous cofactor in various enzyme classes, including PLP-dependent decarboxylases. A recently discovered member of this class is glutamic acid decarboxylase-like protein 1 (GADL1), which lacks the activity to decarboxylate glutamate to γ-aminobutyrate, despite its homology to glutamic acid decarboxylase. Among the acidic amino acid decarboxylases, GADL1 is most similar to cysteine sulfinic acid decarboxylase (CSAD), but the physiological function of GADL1 is unclear, although its expression pattern and activity suggest a role in neurotransmitter and neuroprotectant metabolism.

Mammalian CSAD and GADL1 have distinct biochemical properties and patterns of brain expression.

Variants in the gene encoding the enzyme glutamic acid decarboxylase like 1 (GADL1) have been associated with response to lithium therapy. Both GADL1 and the related enzyme cysteine sulfinic acid decarboxylase (CSAD) have been proposed to be involved in the pyridoxal-5'-phosphate (PLP)-dependent biosynthesis of taurine. In the present study, we compared the catalytic properties, inhibitor sensitivity and expression profiles of GADL1 and CSAD in brain tissue.

Functional properties of rare missense variants of human CDH13 found in adult attention deficit/hyperactivity disorder (ADHD) patients.

The CDH13 gene codes for T-cadherin, a GPI-anchored protein with cell adhesion properties that is highly expressed in the brain and cardiovascular system. Previous studies have suggested that CDH13 may be a promising candidate gene for Attention Deficit/Hyperactivity Disorder (ADHD). The aims of this study were to identify, functionally characterize, and estimate the frequency of coding CDH13 variants in adult ADHD patients and controls.

Attention-deficit/hyperactivity disorder symptoms in offspring of mothers with impaired serotonin production.

Context: Exposure to adverse events during prenatal and postnatal development, as well as serotonin deficiency, have been implicated in disturbances of mood and impulsivity, but the underlying mechanisms are unknown.

Objective: To investigate the long-term effects of an impaired serotonin synthesis on the developing human brain, we studied the effects of nonsynonymous mutations affecting tryptophan hydroxylase (TPH) enzymes responsible for serotonin production in maternal reproductive tissues (TPH1) and the brain (TPH2).

Design: Family-based case-control and functional studies of candidate genes.

Effect of pharmacological chaperones on brain tyrosine hydroxylase and tryptophan hydroxylase 2.

Phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH) and the tryptophan hydroxylases (TPH1 and TPH2) are structurally and functionally related enzymes that share a number of ligands, such as amino acid substrates, pterin cofactors and inhibitors. We have recently identified four compounds (I-IV) with pharmacological chaperone effect for PAH and phenylketonuria mutants (Pey et al. (2008) J.

Activation and stabilization of human tryptophan hydroxylase 2 by phosphorylation and 14-3-3 binding.

TPH (tryptophan hydroxylase) catalyses the rate-limiting step in the synthesis of serotonin, and exists in two isoforms: TPH1, mainly found in peripheral tissues and the pineal body, and TPH2, a neuronal form. In the present study human TPH2 was expressed in Escherichia coli and in HEK (human embryonic kidney)-293 cells and phosphorylated using several different mammalian protein kinases. TPH2 was rapidly phosphorylated to a stoichiometry of 2 mol of phosphate/mol of subunit by PKA (protein kinase A), but only to a stoichiometry of 0.

Brain-specific tryptophan hydroxylase 2 (TPH2): a functional Pro206Ser substitution and variation in the 5'-region are associated with bipolar affective disorder.

The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] controls a broad range of biological functions that are disturbed in affective disorder. In the brain, 5-HT production is controlled by tryptophan hydroxylase 2 (TPH2). In order to assess the possible contribution of TPH2 genetic variability to the aetiology of bipolar affective disorder (BPAD), we systematically investigated common and rare genetic variation in the TPH2 gene through a sequential sequencing and SNP-based genotyping approach.

Characterization of wild-type and mutant forms of human tryptophan hydroxylase 2.

Tryptophan hydroxylase (TPH) catalyses the rate-limiting step in the biosynthesis of serotonin. In vertebrates, the homologous genes tph1 and tph2 encode two different enzymes with distinct patterns of expression, enzyme kinetics and regulation. Variants of TPH2 have recently reported to be associated with reduced serotonin production and behavioural alterations in man and mice.

Sodium butyrate stimulates the synthesis of firefly luciferase in transfected CHO cells but levels of BiP chaperone are unaffected.

A stably transfected CHO cell line (LUCLEAD) was used where the coding region of native Firefly luciferase was linked to the 3'-UTR of the bovine growth hormone, and the 5'-nucleotides coding for the albumin signal peptide were linked to the N-terminal end of the luciferase coding region. Incubation of cells with 1 or 2 mM sodium butyrate (SB) for 72 h had no effect on cell growth since cultures reached confluency at the same time as control cells. Although cell cultures incubated with SB at a concentration of 4 mM were only about 60% confluent the luciferase content was about 5-fold higher than that in control cells.

The serine/threonine kinase Cmk2 is required for oxidative stress response in fission yeast.

Cmk2, a fission yeast Ser/Thr protein kinase homologous to mammalian calmodulin kinases, is essential for oxidative stress response. Cells lacking cmk2 gene were specifically sensitive to oxidative stress conditions. Upon stress, Cmk2 was phosphorylated in vivo, and this phosphorylation was dependent on the stress-activated MAPK Sty1/Spc1.