Polysialic acid directs tumor cell growth by controlling heterophilic neural cell adhesion molecule interactions.
Reads0
Chats0
TLDR
It is established that PSA controls tumor cell growth and differentiation by interfering with NCAM signaling at cell-cell contacts, providing a mechanism for how PSA may promote the genesis and progression of highly aggressive PSA-NCAM-positive tumors.Abstract:
Polysialic acid (PSA), a carbohydrate polymer attached to the neural cell adhesion molecule (NCAM), promotes neural plasticity and tumor malignancy, but its mode of action is controversial. Here we establish that PSA controls tumor cell growth and differentiation by interfering with NCAM signaling at cell-cell contacts. Interactions between cells with different PSA and NCAM expression profiles were initiated by enzymatic removal of PSA and by ectopic expression of NCAM or PSA-NCAM. Removal of PSA from the cell surface led to reduced proliferation and activated extracellular signal-regulated kinase (ERK), inducing enhanced survival and neuronal differentiation of neuroblastoma cells. Blocking with an NCAM-specific peptide prevented these effects. Combinatorial transinteraction studies with cells and membranes with different PSA and NCAM phenotypes revealed that heterophilic NCAM binding mimics the cellular responses to PSA removal. In conclusion, our data demonstrate that PSA masks heterophilic NCAM signals, having a direct impact on tumor cell growth. This provides a mechanism for how PSA may promote the genesis and progression of highly aggressive PSA-NCAM-positive tumors.read more
Citations
More filters
Journal ArticleDOI
Glycosylation in cancer: mechanisms and clinical implications
Salomé S. Pinho,Celso A. Reis +1 more
TL;DR: The roles of glycans are highlighted by the fact that alterations in glycosylation regulate the development and progression of cancer, serving as important biomarkers and providing a set of specific targets for therapeutic intervention.
Journal ArticleDOI
The sweet and sour of cancer: glycans as novel therapeutic targets.
Mark M. Fuster,Jeffrey D. Esko +1 more
TL;DR: A growing body of evidence supports crucial roles for glycans at various pathophysiological steps of tumour progression, and increased understanding of these roles sets the stage for developing pharmaceutical agents that target these molecules.
Journal ArticleDOI
Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology.
Jinwoo Cheon,Jae Hyun Lee +1 more
TL;DR: Each component of such multimodal probes complements the other modalities, and their synergistic materials properties ultimately provide more accurate information in in vitro and in vivo biological systems.
Journal ArticleDOI
Polysialic acid in the plasticity of the developing and adult vertebrate nervous system.
TL;DR: The ability of PSA to increase the plasticity of neural cells is being exploited to improve the repair of adult CNS tissue.
Journal ArticleDOI
Sialic Acids in the Brain: Gangliosides and Polysialic Acid in Nervous System Development, Stability, Disease, and Regeneration
Ronald L. Schnaar,Rita Gerardy-Schahn,Rita Gerardy-Schahn,Herbert Hildebrandt,Herbert Hildebrandt +4 more
TL;DR: In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid as discussed by the authors, which regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules.
References
More filters
Journal ArticleDOI
Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation
TL;DR: Experiments with PC12 cells suggest that the duration of ERK activation is critical for cell signaling decisions, and the extracellular signal-regulated kinase (ERK-regulated) MAPK pathway may be sufficient for these cellular responses.
Journal ArticleDOI
Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing.
Bruce A. Cunningham,John J. Hemperly,Ben A. Murray,Ellen A. Prediger,Robert Brackenbury,Gerald M. Edelman +5 more
TL;DR: The complete amino Acid sequences of the three major polypeptides of N-CAM and most of the noncoding sequences of their messenger RNA's were determined from the analysis of complementary DNA clones and were verified by amino acid sequences of selected CNBr fragments and proteolytic fragments.
Journal ArticleDOI
Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule
TL;DR: The results in a model system demonstrate the large range of binding rates that are obtainable by various forms of local surface modulation of N-CAM, consistent with the proposal that similar alterations affecting (N-C AM)-mediated cell adhesion in vivo may be major factors in pattern formation during development of the nervous system.
Journal ArticleDOI
Polysialic acid in the vertebrate nervous system: a promoter of plasticity in cell-cell interactions.
TL;DR: The ability to perturb PSA in vivo by a specific glycosidase and by the creation of NCAM-deficient mice has led to extensive analysis of its biological function, suggesting that the primary role of PSA is to promote changes in cell interactions and thereby facilitate plasticity in the structure and function of the nervous system.
Journal ArticleDOI
Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination
Brahim Nait-Oumesmar,Laurence Decker,François Lachapelle,Virginia Avellana-Adalid,Corinne Bachelin,Anne Baron-Van Evercooren +5 more
TL;DR: Data indicate that, in addition to the resident population of quiescent oligodendrocyte progenitors of the adult CNS, neural precursors from the adult SVZ constitute a source of oligodendedrocytes for myelin repair.