Signalling pathways involved in the chemotactic activity of CXCL12 in cultured rat cerebellar neurons and CHP100 neuroepithelioma cells

Floridi, Francesca; Trettel, Flavia; Bartolomeo, Sabrina Di; Ciotti, Maria Teresa; Limatola, Cristina

doi:10.1016/s0165-5728(02)00432-0

Cited by 49 publications

(49 citation statements)

References 44 publications

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“…PPPP, DL-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol; GCS, glucosylceramide synthase; GSL, glycosphingolipid; GlcCer, glucosylceramide; GalCer, galactosylceramide; LacCer, lactosylceramide; Gb3, globotriaosylceramide; C 8 …”

Section: Abbreviationsmentioning

confidence: 99%

“…Equal amounts of protein [19] from each sample were processed and analyzed as previously reported [8].…”

Section: Western Blot Analysismentioning

confidence: 99%

“…CXCR4 is a seven-transmembrane-domain receptor coupled to heterotrimeric proteins of the G i family and its engagement by CXCL12 evokes activation of a multiplicity of signalling pathways: among these, activation of phosphoinositide 3-kinase and/or extracellular signal-regulated kinases have been shown to provide key events for chemotaxis induction in a variety of cell systems [3,5,[8][9][10]. Notably, evidence has been provided that signalling through CXCR4 may be sensitive to the receptor lipid environment.…”

Section: Introductionmentioning

confidence: 99%

“…This issue has been herein addressed having as an experimental model the human neuroepithelioma cell line CHP-100 [13]: CXCR4, in fact, is constitutively expressed by CHP-100 cells [14] and, in this system, it has been reported to mediate CXCL12-induced chemotaxis [8].…”

Section: Introductionmentioning

confidence: 99%

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Evidence for a role of glycosphingolipids in CXCR4‐dependent cell migration

et al. 2007

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Chemotaxis induction is a major effect evoked by stimulation of the chemokine receptor CXCR4 with its sole ligand CXCL12. We now report that treatment of CHP-100 human neuroepithelioma cells with the glucosylceramide synthase (GCS) inhibitor DL-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol inhibits CXCR4-dependent chemotaxis. We provide evidence that the phenomenon is not due to unspecific effects of the inhibitor employed and that inhibition of GCS neither affects total or plasmamembrane CXCR4 expression, nor CXCL12-induced Ca 2+ mobilization. The effects of the GCS inhibitor on impairment of CXCL12-induced cell migration temporally correlated with a pronounced downregulation of neutral glycosphingolipids, particularly glucosylceramide, and with a delayed and more moderate downregulation of gangliosides; moreover, exogenously administered glycosphingolipids allowed resumption of CXCR4-dependent chemotaxis. Altogether our results provide evidence, for the first time, for a role glycosphingolipids in sustaining CXCL12-induced cell migration.

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Section: Abbreviationsmentioning

confidence: 99%

“…Equal amounts of protein [19] from each sample were processed and analyzed as previously reported [8].…”

Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evidence for a role of glycosphingolipids in CXCR4‐dependent cell migration

et al. 2007

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“…Stromal cell-derived factor-1a (SDF-1a), now also named CXCL12, belongs to the CXC subfamily and is a ligand for the G-protein-coupled receptor CXCR4. The binding of CXCL12 to CXCR4 activates multiple signaling pathways, including the extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase-Akt, cAMP/ cAMP-dependent protein kinase, and phospholipase C pathways, and results in increased intracellular calcium levels and the release of cytokines by glial cells [8][9][10]. Increasing evidence suggests that CXCL12/CXCR4 play important roles in nociceptive signal processing [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

Bai

Wang

et al. 2016

Neurosci. Bull.

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Emerging evidence indicates that CXCL12/ CXCR4 signaling is involved in chronic pain. However, few studies have systemically assessed its role in direct nerve injury-induced neuropathic pain and the underlying mechanism. Here, we determined that spared nerve injury (SNI) increased the expression of CXCL12 and its cognate receptor CXCR4 in lumbar 5 dorsal root ganglia (DRG) neurons and satellite glial cells. SNI also induced longlasting upregulation of CXCL12 and CXCR4 in the ipsilateral L4-5 spinal cord dorsal horn, characterized by CXCL12 expression in neurons and microglia, and CXCR4 expression in neurons and astrocytes. Moreover, SNIinduced a sustained increase in TNF-a expression in the DRG and spinal cord. Intraperitoneal injection (i.p.) of the TNF-a synthesis inhibitor thalidomide reduced the SNI-induced mechanical hypersensitivity and inhibited the expression of CXCL12 in the DRG and spinal cord. Intrathecal injection (i.t.) of the CXCR4 antagonist AMD3100, both 30 min before and 7 days after SNI, reduced the behavioral signs of allodynia. Rats given an i.t. or i.p. bolus of AMD3100 on day 8 of SNI exhibited attenuated abnormal pain behaviors. The neuropathic pain established following SNI was also impaired by i.t. administration of a CXCL12-neutralizing antibody. Moreover, repetitive i.t. AMD3100 administration prevented the activation of ERK in the spinal cord. The mechanical hypersensitivity induced in naïve rats by i.t. CXCL12 was alleviated by pretreatment with the MEK inhibitor PD98059. Collectively, our results revealed that TNF-a might mediate the upregulation of CXCL12 in the DRG and spinal cord following SNI, and that CXCL12/CXCR4 signaling via ERK activation contributes to the development and maintenance of neuropathic pain.

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A distinct subset of glioma cell lines with stem cell‐like properties reflects the transcriptional phenotype of glioblastomas and overexpresses CXCR4 as therapeutic target

Schulte

Günther

Phillips³

et al. 2011

Glia

101

137

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Glioblastomas contain stem-like cells that can be maintained in vitro using specific serum-free conditions. We investigated whether glioblastoma stem-like (GS) cell lines preserve the expression phenotype of human glioblastomas more closely than conventional glioma cell lines. Expression profiling revealed that a distinct subset of GS lines, which displayed a full stem-like phenotype (GSf), mirrored the expression signature of glioblastomas more closely than either other GS lines or cell lines grown in serum. GSf lines are highly tumorigenic and invasive in vivo, express CD133, grow spherically in vitro, are multipotent and display a Proneural gene expression signature, thus recapitulating key functional and transcriptional aspects of human glioblastomas. In contrast, GS lines with a restricted stem-like phenotype exhibited expression signatures more similar to conventional cell lines than to original patient tumors, suggesting that the transcriptional resemblance between GS lines and tumors is associated with different degrees of "stemness". Among markers overexpressed in patient tumors and GSf lines, we identified CXCR4 as a potential therapeutic target. GSf lines contained a minor population of CXCR4(hi) cells, a subfraction of which coexpressed CD133 and was expandable by hypoxia, whereas conventional cell lines contained only CXCR4(lo) cells. Convection-enhanced local treatment with AMD3100, a specific CXCR4 antagonist, inhibited the highly invasive growth of GS xenografts in vivo and cell migration in vitro. We thus demonstrate the utility of GSf lines in testing therapeutic agents and validate CXCR4 as a target to block the growth of invasive tumor-initiating glioma stem cells in vivo.

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Signalling pathways involved in the chemotactic activity of CXCL12 in cultured rat cerebellar neurons and CHP100 neuroepithelioma cells

Cited by 49 publications

References 44 publications

Evidence for a role of glycosphingolipids in CXCR4‐dependent cell migration

Evidence for a role of glycosphingolipids in CXCR4‐dependent cell migration

Upregulation of Chemokine CXCL12 in the Dorsal Root Ganglia and Spinal Cord Contributes to the Development and Maintenance of Neuropathic Pain Following Spared Nerve Injury in Rats

A distinct subset of glioma cell lines with stem cell‐like properties reflects the transcriptional phenotype of glioblastomas and overexpresses CXCR4 as therapeutic target

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