Remco van Horssen

Radboud University | RU · Department of Cell and Applied Biology

Oncogenic transformation involves reprogramming of cell metabolism, whereby steady-state levels of intracellular NAD(+) and NADH can undergo dramatic changes while ATP concentration is generally well maintained. Altered expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD(+)-salvage, accompanies the changes...

Transformed cancer cells have an altered metabolism, characterized by a shift towards aerobic glycolysis, referred to as 'the Warburg phenotype'. A change in flux through mitochondrial OXPHOS and cytosolic pathways for ATP production and a gain of capacity for biomass production in order to sustain the needs for altered growth and morphodynamics ar...

Inactivation of the tumor suppressor E-cadherin is an important event during breast tumorigenesis, as its decreased expression is linked to aggressiveness and metastasis. However, the relationship between the different modes of E-cadherin inactivation (mutation versus promotor hypermethylation) and breast cancer cell behavior is incompletely unders...

TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients...

When highly invasive cancer cells are cultured on an extracellular matrix substrate, they extend proteolytically active membrane protrusions, termed invadopodia, from their ventral surface into the underlying matrix. Our understanding of the molecular composition of invadopodia has rapidly advanced in the last few years, but is far from complete. T...

DMPK, the product of the mutated gene in myotonic dystrophy type 1, belongs to the subfamily of Rho-associated serine-threonine protein kinases, whose members play a role in actin-based cell morphodynamics. Not much is known about the physiological role of differentially localized individual DMPK splice isoforms. We report here that prominent stell...

In our body cells move in three dimensions, embedded in an extracellular matrix that varies in composition, density and stiffness, and this movement is fundamental to life. Next to 3D cell migration assays, representing these physiological circumstances, still we need 2D migrations assays to perform detailed studies on the contribution of matrix-co...

The natural environment of a living cell is not only organized on a micrometer, but also on a nanometer scale. Mimicking such a nanoscale topography in implantable biomaterials is critical to guide cellular behavior. Also, a correct positioning of cells on biomaterials is supposed to be very important for promoting wound healing and tissue regenera...

Rapalog-induced membrane localization of CK-B and CK-BC238S in MEFs. (A) MEF-BAK−/− cells stably expressing MYR-FKBP were retrovirally transduced with FRB-CK-B (upper panels) or CK-BC283S (lower panels) and stained for CK-B. Rapalog treatment (100 nM, 1 h, left panels) resulted in translocation of (a fraction of) CK-B and CK-BC283S to cellular memb...

Morphology measurements of migrating MEFs. In the top panel, the analysis of migration morphology is illustrated. The number of lamellipodia per cell, the lamellipodium dimensions (width and length measured with cell body as reference, lamellipodium includes lamella-region) and tail length was measured. Lower panels show high magnification images o...

CK-B mediates astrocyte migration. WT (upper panels) and CK-B−/− (lower panels) astrocytes migrating along laminin for 48 h. Migration assays were performed without (left panels) and with (right panels) cyclocreatine treatment. Both CK-B knockout and inhibition strongly decreased migratory behavior of astrocytes. Video S1 corresponds with Figure 4A...

Cyclocreatine does not alter proliferation and apoptosis. A) Proliferation of MEF-CK-B (left) and MEF-MYR-CK-B (right) cells with (red) and without (black) cCr (5 mM) treatment. Relative proliferation rates, taking non-treated cells as control, are shown of three independent experiments. (B) Apoptosis of MEF-CK-B and MEF-MYR-CK-B cells cultured wit...

MEF-MYR-CK-B cells spread out faster than MEF-CK-B cells. Quantification of MEF spreading on FN for 30 min, showing that expression of MYR-CK-B facilitates cell spreading. * p<0.05. (0.68 MB TIF)

CK-B expression and localization affects MEF migration. YFP/MYR-YFP complemented (upper panels) and CK-B/MYR-CK-B complemented MEFs migration along FN for 24 h. Migration assays of non-targeted (left panels) and membrane-targeted (right panels) cells showed that CK-B induced migration and additionally that MEF-MYR-CK-B were the most motile. Video S...

Cyclocreatine selectively inhibits CK-B-induced migration. MEF-YFP, MEF-CK-B, MEF-MYR-CK-B and MEK-AK1 cells were followed during migration along FN. In contrast to YFP and AK1 complemented MEFs, MEF-CK-B and MEF-MYR-CK-B migration was inhibited by cCr and a strong morphological effect was observed. Video S3 corresponds with Figure 6C. Time-lapse p...

Repositioning of CK-B to cellular membranes induces migration. MEF-MYR-FKBP cells transfected with FRB-CK-B (upper panels) or FRB-CK-BC283s (lower panels) were allowed to migrate along FN without (left panels) and with Rapalog (right panels). Rapalog-mediated targeting of CK-B to membranes, but not CK-BC283s membrane targeting, stimulated migration...

Creatine Kinases (CK) catalyze the reversible transfer of high-energy phosphate groups between ATP and phosphocreatine, thereby playing a storage and distribution role in cellular energetics. Brain-type CK (CK-B) deficiency is coupled to loss of function in neural cell circuits, altered bone-remodeling by osteoclasts and complement-mediated phagocy...

ATP is the "principal energy currency" in metabolism and the most versatile small molecular regulator of cellular activities. Although already much is known about the role of ATP in fundamental processes of living systems, data about its compartmentalization are rather scarce, and we still have only very limited understanding of whether patterns in...

Endothelial monocyte-activating polypeptide-II (EMAP-II), a proinflammatory cytokine with antiangiogenic properties, renders tumours sensitive to tumour necrosis factor-alpha (TNF) treatment. The exact mechanisms for this effect remain unclear. Here we show that human endothelial cells (EC) are insensitive to TNF-induced apoptosis but after a short...

Cell migration is crucial in virtually every biological process and strongly depends on the nature of the surrounding matrix. An assay that enables real-time studies on the effects of defined matrix components and growth factors on cell migration is not available. We have set up a novel, quantitative migration assay, which enables unharmed cells to...

In motile fibroblasts, stable microtubules (MTs) are oriented toward the leading edge of cells. How these polarized MT arrays are established and maintained, and the cellular processes they control, have been the subject of many investigations. Several MT "plus-end-tracking proteins," or +TIPs, have been proposed to regulate selective MT stabilizat...

Endothelial monocyte-activating polypeptide-II (EMAP-II) is a pro-inflammatory cytokine with anti-angiogenic properties. Its precursor, proEMAP, is identical to the p43 auxiliary component of the tRNA multisynthetase complex and therefore involved in protein translation. Although most of the activities have been ascribed to the active form EMAP-II,...

Tumour necrosis factor-alpha (TNF) has been used in the clinic for more than 10 years in an isolated limb perfusion (ILP). However, intra-tumoural expression of TNF receptor-1 (TNF-R1) and TNF-R1 upregulating factors are unknown. We determined the expression of TNF-R1, proEMAP and endothelial monocyte-activating polypeptide-II (EMAP-II) before and...

Learning Objectives After completing this course, the reader will be able to: Discuss the role of TNF-a in cancer survival and apoptosis.Describe the mechanism of chemotherapy potentiation by TNF-a.Explain the selective targeting of tumor vasculature by TNF-a.Discuss TNFR-1 and TNFR-2 signaling. Access and take the CME test online and receive 1 AMA...

In 1990 Clauss et al. first reported on a 44-kDa polypeptide, later called Endothelial Monocyte Activating Polypeptide II (EMAP II). This protein was discovered in the supernatant of Meth-A fibrosarcoma cells and was shown to enhance the induction of the procoagulant Tissue Factor (TF) on endothelial cells. Besides up-regulation of TF mRNA, EMAP II...

Experiments with tumor necrosis factor alpha (TNF) in rodents have shown that a high dose can lead to hemorrhagic necrosis in tumors. Endothelial monocyte-activating polypeptide II (EMAP-II) is a novel tumor-derived cytokine, and its expression increases the TNF-1 receptor on tumor endothelium, enhances the induction of tissue factor on tumor endot...