A novel process for transcellular hemoglobin transport from macrophages to cancer cells.

Hemoglobin (Hb) performs its physiological function within the erythrocyte. Extracellular Hb has prooxidative and proinflammatory properties and is therefore sequestered by haptoglobin and bound by the CD163 receptor on macrophages. In the present study, we demonstrate a novel process of Hb uptake by macrophages independent of haptoglobin and CD163.

Iron-triggered signaling via ETS1 and the p38/JNK MAPK pathway regulates Bmp6 expression.

BMP6 is an iron-sensing cytokine whose transcription in liver sinusoidal endothelial cells (LSECs) is enhanced by high iron levels, a step that precedes the induction of the iron-regulatory hormone hepcidin. While several reports suggested a cell-autonomous induction of Bmp6 by iron-triggered signals, likely via sensing of oxidative stress by the transcription factor NRF2, other studies proposed the dominant role of a paracrine yet unidentified signal released by iron-loaded hepatocytes. To further explore the mechanisms of Bmp6 transcriptional regulation, we used female mice aged 10-11 months, which are characterized by hepatocytic but not LSEC iron accumulation, and no evidence of systemic iron overload.

Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options.

The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe and the USA in recent decades. Among the different subtypes of liver cancers, hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer. Besides advances in diagnosis and promising results of pre-clinical studies, HCC remains a highly lethal disease.

The CD200 Regulates Inflammation in Mice Independently of TNF-α Production.

Inflammatory bowel disease is characterized by the infiltration of immune cells and chronic inflammation. The immune inhibitory receptor, CD200R, is involved in the downregulation of the activation of immune cells to prevent excessive inflammation. We aimed to define the role of CD200R ligand-CD200 in the experimental model of intestinal inflammation in conventionally-reared mice.

The Role of Macrophages in Cancer Development and Therapy.

Macrophages are critical mediators of tissue homeostasis and influence various aspects of immunity. Tumor-associated macrophages are one of the main cellular components of the tumor microenvironment. Depending on their activation status, macrophages can exert a dual influence on tumorigenesis by either antagonizing the cytotoxic activity of immune cells or, less frequently, by enhancing antitumor responses.

Biodistribution PET/CT Study of Hemoglobin-DFO-Zr Complex in Healthy and Lung Tumor-Bearing Mice.

Proteins, as a major component of organisms, are considered the preferred biomaterials for drug delivery vehicles. Hemoglobin (Hb) has been recently rediscovered as a potential drug carrier, but its use for biomedical applications still lacks extensive investigation. To further explore the possibility of utilizing Hb as a potential tumor targeting drug carrier, we examined and compared the biodistribution of Hb in healthy and lung tumor-bearing mice, using for the first time Zr labelled Hb in a positron emission tomography (PET) measurement.

The pro-tumor effect of CD200 expression is not mimicked by agonistic CD200R antibodies.

Tumor-infiltrating immune cells can impact tumor growth and progression. The inhibitory CD200 receptor (CD200R) suppresses the activation of myeloid cells and lack of this pathway results in a reduction of tumor growth, conversely a tumorigenic effect of CD200R triggering was also described. Here we investigated the role of CD200R activation in syngeneic mouse tumor models.

Antitumor Activity of TLR7 Is Potentiated by CD200R Antibody Leading to Changes in the Tumor Microenvironment.

Stimulation of Toll-like receptor 7 (TLR7) activates myeloid cells and boosts the immune response. Previously, we have shown that stimulation of the inhibitory CD200 receptor (CD200R) suppresses TLR7 signaling and that the absence of CD200R signaling leads to a decreased number of papillomas in mice. Here, we investigated the effects of agonistic anti-CD200R on the antitumor activity of a TLR7 agonist (R848) in a syngeneic mouse tumor model.

Evaluation of phenotypic and functional stability of RAW 264.7 cell line through serial passages.

Established cell lines are widely used in research, however an appealing question is the comparability of the cells between various laboratories, their characteristics and stability in time. Problematic is also the cell line misidentification, genetic and phenotypic shift or Mycoplasma contamination which are often forgotten in research papers. The monocyte/macrophage-like cell line RAW 264.

Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions.

Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure.

Astrocyte-neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes.

Astrocytes releasing glucose- and/or glycogen-derived lactate and glutamine play a crucial role in shaping neuronal function and plasticity. Little is known, however, how metabolic functions of astrocytes, e.g.