1,721,060 research outputs found

    Proteoglycan control of cell movement during wound healing and cancer spreading

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    By virtue of their multifunctional nature, proteoglycans (PGs) are thought to govern the process of cell movement in numerous physiological and pathological contexts, spanning from early embryonic development to tumour invasion and metastasis. The precise mode by which they influence this process is still fragmentary, but evidence is accruing that they may affect it in a multifaceted manner. PGs bound to the plasma membrane mediate the polyvalent interaction of the cell with matrix constituents and with molecules of the neighbouring cells' surfaces; they modulate the activity of receptors implicated in the recognition of these components; and they participate in the perception and convergence of growth- and motility-promoting cues contributed by soluble factors. Through some of these interactions several PGs transduce to pro-motile cells crucial intracellular signals that are likely to be essential for their mobility. A regulated shedding of certain membrane-intercalated PGs seems to provide an additional level of control of cell movement. Coincidentally, matrix-associated PGs may govern cell migration by structuring permissive and non-permissive migratory paths and, when directly secreted by the moving cells, may alternatively create favourable or hostile microenvironments. To exert this latter, indirect effect on cell movement, matrix PGs strongly rely upon their primary molecular partners, such as hyaluronan, link proteins, tenascins, collagens and low-affinity cell surface receptors, whereas a further finer control is provided by a highly regulated proteolytic processing of the PGs accounted by both the migrating cells themselves and cells of their surrounding tissues. Overall, PGs seem to play an important role in determining the migratory phenotype of a cell by initiating, directing and terminating cell movement in a spatio-temporally controlled fashion. This implies that the "anti-adhesive and/or "anti-migratory" properties that have previously been assigned to certain PGs may be re-interpreted as being a means by which these macromolecules elaborate haptotaxis-like mechanisms imposing directionality upon the moving cells. Since these conditions would allow cells to be led to given tissue locations and become immobilized at these sites, a primary function may be ascribed to PGs in the dictation of a "stop or go" choice of the migrating cells. © 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved

    Neurogenic potential of human mesenchymal stem cells revisited: analysis by immunostaining, time-lapse video and microarray.

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    The possibility of generating neural cells from human bone-marrow-derived mesenchymal stem cells (hMSCs) by simple in vitro treatments is appealing both conceptually and practically. However, whether phenotypic modulations observed after chemical manipulation of such stem cells truly represent a genuine trans-lineage differentiation remains to be established. We have re-evaluated the effects of a frequently reported biochemical approach, based on treatment with butylated hydroxyanisole and dimethylsulphoxide, to bring about such phenotypic conversion by monitoring the morphological changes induced by the treatment in real time, by analysing the expression of phenotype-specific protein markers and by assessing the modulation of transcriptome. Video time-lapse microscopy showed that conversion of mesenchymal stem cells to a neuron-like morphology could be reproduced in normal primary fibroblasts as well as mimicked by addition of drugs eliciting cytoskeletal collapse and disruption of focal adhesion contacts. Analysis of markers revealed that mesenchymal stem cells constitutively expressed multi-lineage traits, including several pertaining to the neural one. However, the applied ;neural induction' protocol neither significantly modulated the expression of such markers, nor induced de novo translation of other neural-specific proteins. Similarly, global expression profiling of over 21,000 genes demonstrated that gene transcription was poorly affected. Most strikingly, we found that the set of genes whose expression was altered by the inductive treatment did not match those sets of genes differentially expressed when comparing untreated mesenchymal stem cells and immature neural tissues. Conversely, by comparing these gene expression profiles with that obtained from comparisons between the same cells and an unrelated non-neural organ, such as liver, we found that the adopted neural induction protocol was no more effective in redirecting human mesenchymal stem cells toward a neural phenotype than toward an endodermal hepatic pathway

    Pro-apoptotic anti-NG2/CSPG4 antibodies and their uses in disease therapy

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    The present invention relates to an antibody capable of binding with highaffinity and high selectivity to the ectodomain of the transmembrane proteoglycan (PG) NG2/CSPG4. The invention specifically refers to said antibody possessing the ability to uniquely induce programmed cell death through canonical caspase-dependent apoptosis or authophagy, 5 in cancer cells specifically expressing such protein, and without the participation of other exogenously added factors. Moreover, the present invention refers to a composition comprising the antibody of the invention as pharmaceutical excipients
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