L’ostéopontine, une molécule aux multiples facettes

Chabas, Dorothée

doi:10.1051/medsci/20052110832

Cited by 32 publications

(9 citation statements)

References 66 publications

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“…It is an arginine-glycine-aspartic acid (RGD) containing extracellular matrix protein with diverse functions [8,9]. OPN interaction with integrin αvβ3 transduces cell-matrix signaling directed to increased motility, invasion, and angiogenesis [10].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Erk1/2 activation by osteopontin in PC3 human prostate cancer cells

2010

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BackgroundOsteopontin (OPN) has been shown to play many roles in the progression of cancer. We have recently demonstrated the activation of Akt by OPN. Integrin-linked kinase and PI3-kinase are integral proteins in OPN/AKT pathway in PC3 cells. To investigate the role of the extracellular receptors in OPN signaling, we have examined the spatio-temporal regulation of CD44 and integrin αvβ3 receptor in OPN-induced Akt activation in PC3 cells.ResultsHere, our studies demonstrate that OPN can activate Akt either through the αVβ3 integrin or the CD44 cell surface receptor. Members of the Mitogen Activated Protein Kinase (MAPK) family have been shown to be up-regulated in a variety of human cancers and have been implicated in the metastatic behavior. Our studies have demonstrated an increase in the phosphorylation of c-Raf at Ser259 and Ser338 in PC3 cells over-expressing OPN. This increase matches up with the Erk1/2 phosphorylation at Thr202/204 and activation. However, the inhibition of Akt activity augments the phosphorylation state of ERK1/2 to two to three fold with a concomitant reduction in the phosphorylation state of c-Raf at Ser259.ConclusionsRegulation c-Raf phosphorylation at Ser259 has a role in the anti-apoptotic pathways mediated by Akt or Raf/MEK/ERK proteins. OPN may have dual effects in the activation of Erk1/2. We propose this based on the observations that while OPN activates c-Raf and Erk1/2; it also acts to inhibit c-Raf and Erk1/2 activation through Akt pathway. Our observations suggest that the activation of c-Raf-ERK cascade may promote cell cycle arrest in prostate cancer cells and OPN signaling has a role in the anti-apoptotic mechanism.

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Section: Introductionmentioning

confidence: 99%

Regulation of Erk1/2 activation by osteopontin in PC3 human prostate cancer cells

2010

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“…C3a anaphylatoxin is involved in inflammatory processes following focal cerebral ischemia [45] and has been described as a chemotactic factor for mesenchymal stem cells in vitro [46]. Similarly, SPP1, also called osteopontin, exhibits strong chemoattractive and proinflammatory properties [47], is upregulated in injured brain areas [48, 49], and promotes the migration of various cell types, including astrocytes, mesenchymal stem cells, or neuroblasts from the subventricular zone [48, 50–53]. CXCL10, a member of the CXC chemokine family, can also attract bone marrow-derived mesenchymal stem cells (BM-MSCs) [54], and CXCL10-expressing cells appear in the inflamed central nervous system after a trauma or in neurodegenerative diseases [55].…”

Section: Discussionmentioning

confidence: 99%

“…This comparison highlights the high sensitivity of human OE-MSCs to SPP1. This cytokine is known to interact with different cell surface receptors [47] such as integrin β1 [51, 53] and integrin α v [49] via an arginine-glycine-aspartate (RGD) domain or with CD44 via an RGD-independent mechanism [50]. In a previous study [11], we demonstrated that human OE-MSCs strongly express integrin β 1 (CD29), integrin α v (CD51), and CD44 at their surface.…”

Section: Discussionmentioning

confidence: 99%

From Blood to Lesioned Brain: An In Vitro Study on Migration Mechanisms of Human Nasal Olfactory Stem Cells

Girard

Virard

Lacassagne

et al. 2017

Stem Cells International

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Stem cell-based therapies critically rely on selective cell migration toward pathological or injured areas. We previously demonstrated that human olfactory ectomesenchymal stem cells (OE-MSCs), derived from an adult olfactory lamina propria, migrate specifically toward an injured mouse hippocampus after transplantation in the cerebrospinal fluid and promote functional recoveries. However, the mechanisms controlling their recruitment and homing remain elusive. Using an in vitro model of blood-brain barrier (BBB) and secretome analysis, we observed that OE-MSCs produce numerous proteins allowing them to cross the endothelial wall. Then, pan-genomic DNA microarrays identified signaling molecules that lesioned mouse hippocampus overexpressed. Among the most upregulated cytokines, both recombinant SPP1/osteopontin and CCL2/MCP-1 stimulate OE-MSC migration whereas only CCL2 exerts a chemotactic effect. Additionally, OE-MSCs express SPP1 receptors but not the CCL2 cognate receptor, suggesting a CCR2-independent pathway through other CCR receptors. These results confirm that OE-MSCs can be attracted by chemotactic cytokines overexpressed in inflamed areas and demonstrate that CCL2 is an important factor that could promote OE-MSC engraftment, suggesting improvement for future clinical trials.

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“…D'autres travaux montrent, par ailleurs, que la tétraspanine CD9 pourrait avoir un rôle suppresseur de métastases. En effet, la régulation négative de son expression par l'ostéopontine [45] (➜) conduit à une augmentation des capacités invasives des cellules de mélanome primitif dans des systèmes de transmigration en matrice de collagène [35]. Il est donc tout à fait possible que la fonction promotrice, ou activatrice de métastases, de la tétraspanine CD9 dans le mélanome dépende des partenaires qui lui sont associés, et qui peuvent différer au cours des étapes de la progression tumorale.…”

Section: Les Tétraspanines Des Mélanocytesunclassified

Les tétraspanines dans la physiopathologie de la peau

2016

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> Les tétraspanines sont des protéines transmembranaires qui interagissent entre elles et avec d'autres protéines telles que des intégrines, des protéines à domaines immunoglobulines, des récepteurs à facteurs de croissance et à cytokines. Elles participent ainsi à l'organisation de réseaux de signalisation à la membrane plasmique des cellules. Bien qu'elles soient exprimées abondamment et souvent de façon ubiquitaire, leur fonction a été peu étudiée à ce jour. Il est toutefois bien établi qu'elles régulent l'adhésion cellulaire, la migration, l'invasion, la survie ou l'infection par les virus. Les mécanismes moléculaires sous-jacents restent cependant à élucider. Nous exposerons dans cette revue quelles sont les différentes tétraspanines exprimées par les cellules de l'épiderme et quels rôles elles jouent dans la physiopathologie cutanée, et en particulier dans la cancérogenèse. < Bien qu'un nombre restreint de membres de cette famille ait été étu-dié, il apparaît aujourd'hui que les fonctions des tétraspanines soient majoritairement déterminées par les interactions latérales qu'elles établissent à la surface cellulaire. En effet, les tétraspanines ont la particularité d'interagir entre elles et avec d'autres protéines membranaires pour former des microdomaines membranaires spécialisés, appelés « réseaux tétraspanines », qui sont fonctionnellement distincts des radeaux lipidiques [1, 3,4]. Les interactions avec leurs partenaires membranaires peuvent être directes ou indirectes, recrutant alors des molécules de signalisation intracellulaire qui vont conduire à la mise en place de véritables plateformes de signalisation au niveau de la membrane plasmique. Les tétraspanines interviennent ainsi dans de nombreux processus cellulaires, physiologiques et pathologiques, parmi lesquels la migration, l'invasion, la fusion des gamètes, la réponse inflammatoire, etc.

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L’ostéopontine, une molécule aux multiples facettes

Cited by 32 publications

References 66 publications

Regulation of Erk1/2 activation by osteopontin in PC3 human prostate cancer cells

Regulation of Erk1/2 activation by osteopontin in PC3 human prostate cancer cells

From Blood to Lesioned Brain: An In Vitro Study on Migration Mechanisms of Human Nasal Olfactory Stem Cells

Les tétraspanines dans la physiopathologie de la peau

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