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Träfflista för sökning "WFRF:(Forsberg Karin) ;pers:(Kundu Soumi)"

Sökning: WFRF:(Forsberg Karin) > Kundu Soumi

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1.
  • Forsberg, Maud, et al. (författare)
  • Undersulfation of Heparan Sulfate Restricts Differentiation Potential of Mouse Embryonic Stem Cells
  • 2012
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:14, s. 10853-10862
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparan sulfate proteoglycans, present on cell surfaces and in the extracellular matrix, interact with growth factors and morphogens to influence growth and differentiation of cells. The sulfation pattern of the heparan sulfate chains formed during biosynthesis in the Golgi compartment will determine the interaction potential of the proteoglycan. The glucosaminyl N-deacetylase/N-sulfotransferase (NDST) enzymes have a key role during biosynthesis, greatly influencing total sulfation of the heparan sulfate chains. The differentiation potential of mouse embryonic stem cells lacking both NDST1 and NDST2 was studied using in vitro differentiation protocols, expression of differentiation markers, and assessment of the ability of the cells to respond to growth factors. The results show that NDST1 and NDST2 are dispensable for mesodermal differentiation into osteoblasts but necessary for induction of adipocytes and neural cells. Gene expression analysis suggested a differentiation block at the primitive ectoderm stage. Also, GATA4, a primitive endoderm marker, was expressed by these cells. The addition of FGF4 or FGF2 together with heparin rescued the differentiation potential to neural progenitors and further to mature neurons and glia. Our results suggest that the embryonic stem cells lacking both NDST1 and NDST2, expressing a very low sulfated heparan sulfate, can take the initial step toward differentiation into all three germ layers. Except for their potential for mesodermal differentiation into osteoblasts, the cells are then arrested in a primitive ectoderm and/or endoderm stage.
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  • Xiong, Anqi, 1986-, et al. (författare)
  • Heparanase confers a growth advantage to differentiating murine embryonic stem cells, and enhances oligodendrocyte formation.
  • 2017
  • Ingår i: Matrix Biology. - : Elsevier BV. - 0945-053X .- 1569-1802. ; 62, s. 92-104
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells, play important roles in development and homeostasis. These molecules are located primarily on the cell surface and in the pericellular matrix, where they interact with a multitude of macromolecules, including many growth factors. Manipulation of the enzymes involved in biosynthesis and modification of HSPG structures alters the properties of stem cells. Here, we focus on the involvement of heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in differentiation of embryonic stem cells into the cells of the neural lineage. Embryonic stem (ES) cells overexpressing HPSE (Hpse-Tg) proliferated more rapidly than WT ES cells in culture and formed larger teratomas in vivo. In addition, differentiating Hpse-Tg ES cells also had a higher growth rate, and overexpression of HPSE in NSPCs enhanced Erk and Akt phosphorylation. Employing a two-step, monolayer differentiation, we observed an increase in HPSE as wild-type (WT) ES cells differentiated into neural stem and progenitor cells followed by down-regulation of HPSE as these NSPCs differentiated into mature cells of the neural lineage. Furthermore, NSPCs overexpressing HPSE gave rise to more oligodendrocytes than WT cultures, with a concomitant reduction in the number of neurons. Our present findings emphasize the importance of HS, in neural differentiation and suggest that by regulating the availability of growth factors and, or other macromolecules, HPSE promotes differentiation into oligodendrocytes.
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  • Kitambi, Satish Srinivas, et al. (författare)
  • Vulnerability of Glioblastoma Cells to Catastrophic Vacuolization and Death Induced by a Small Molecule
  • 2014
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 157:2, s. 313-328
  • Tidskriftsartikel (refereegranskat)abstract
    • Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer with marginal life expectancy. Based on the assumption that GBM cells gain functions not necessarily involved in the cancerous process, patient-derived glioblastoma cells (GCs) were screened to identify cellular processes amenable for development of targeted treatments. The quinine-derivative NSC13316 reliably and selectively compromised viability. Synthetic chemical expansion reveals delicate structure-activity relationship and analogs with increased potency, termed Vacquinols. Vacquinols stimulate death by membrane ruffling, cell rounding, massive macropinocytic vacuole accumulation, ATP depletion, and cytoplasmic membrane rupture of GCs. The MAP kinase MKK4, identified by a shRNA screen, represents a critical signaling node. Vacquinol-1 displays excellent in vivo pharmacokinetics and brain exposure, attenuates disease progression, and prolongs survival in a GBM animal model. These results identify a vulnerability to massive vacuolization that can be targeted by small molecules and point to the possible exploitation of this process in the design of anticancer therapies.
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  • Kundu, Soumi, et al. (författare)
  • Glycosaminoglycans and Glioma Invasion
  • 2014
  • Ingår i: European Association of NeuroOncology Magazine. - : Krause & Pachernegg GmbH. - 2224-3453. ; 4:2, s. 75-80
  • Forskningsöversikt (refereegranskat)abstract
    • There is a great need for novel therapiesto target malignant glioma, a disease withan often dismal prognosis. One of the hallmarksof malignant glioma is its effi cient invasion of thehealthy brain parenchyma, which leads to rapidlyrecurrent disease upon surgical removal of theoriginal tumour. To be able to establish new tumoursat a distance from the original neoplasm,glioma cells must detach, migrate through themicroenvironment, settle, and proliferate in theirnew location. This includes changing adhesivecharacteristics, breaking down extracellular matrixmolecules (ECM), and perturbed growth factorsignalling. Investigations of the glioma-specificECM composition may therefore provide newinsights into glioma infi ltration. In this review, wefocus on glycosaminoglycans, important componentsof the ECM that are long unbranched polysaccharidescomposed of repeating disaccharideunits. We discuss the roles for hyaluronan, one ofthe major brain ECM molecules, and that of theproteoglycans, heparan sulphate proteoglycans(HSPG) and chondroitin sulphate proteoglycans(CSPG), in glioma biology. Heparan sulphate (HS)and chondroitin sulphate (CS) chains act togetherwith a wide variety of bioactive molecules, andthese interactions depend on the HS and CS sulphationpatterns. HS and CS chain modifi cationsare implicated not only in normal developmentand homoeostasis but they also play importantroles in pathological conditions including cancer.Dysregulated glycosaminoglycans, their biosyntheticand degradation enzymes as well as theproteoglycan core proteins are known to affectseveral stages of tumour progression, angiogenesis,and metastasis. Finding the specifi c characteristicsof tumour cells that confer this infi ltrativecapacity of glioma may offer new avenuesfor drug development.
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