Stromal cell‐derived factor 1α (SDF‐1α) induces gene‐expression of early growth response‐1 (Egr‐1) and VEGF in human arterial endothelial cells and enhances VEGF induced cell proliferation

Neuhaus, Thomas J.; Stier, Sebastian; Totzke, Gudrun; Gruenewald, Elisabeth; Fronhoffs, Stefan; Sachinidis, Agapios; Vetter, Hans; Ko, Yon

doi:10.1046/j.1365-2184.2003.00262.x

Cited by 72 publications

(54 citation statements)

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“…Activation of CXCR4 in human megakaryoblasts led to the phosphorylation of the nuclear transcription factor Elk (Majka et al, 2000). Likewise, Egr-1 expression was increased by SDF-1 in arterial endothelial cells, thus enhancing vascular endothelial growth factor-mediated cell proliferation (Neuhaus et al, 2003). Both of these observations imply nuclear translocation of ERK, but this has not been experimentally confirmed.…”

mentioning

confidence: 55%

Regulation of CXCR4-Mediated Nuclear Translocation of Extracellular Signal-Related Kinases 1 and 2

et al. 2005

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Activation of the chemokine receptor CXCR4 by its agonist stromal cell-derived factor 1 (SDF-1) has been associated with cell migration and proliferation in many cell types, but the intracellular signaling cascades are incompletely defined. Here we show that CXCR4-dependent extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation was mediated through the Ras/Raf pathway, as demonstrated with a dominant-negative Ras mutant and pharmacological inhibitors. The Src inhibitor 4-amino-5-methylphenyl-7-(t-butyl)pyrazolo [3,4-d] pyrimidine (PP1) and the Rho-kinase (ROCK) inhibitor N-(4-pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide dihydrochloride (Y27632) also attenuated SDF-1-induced ERK1/2 phosphorylation. Involvement of Src could furthermore be demonstrated by Src phosphorylation and by the shortened ERK1/2 phosphorylation in SYF cells, which are Src/Yes/Fyndeficient compared with Src-reconstituted Src ϩϩ cells. Membrane translocation of RhoA could be detected similarly. A large portion of the SDF-1-mediated ERK phosphorylation was detected in the nucleus, as shown by Western blotting and confocal microscopy, and resulted in the phosphorylation of the transcription factor Elk. It is interesting that the nuclear accumulation of ERK1/2 and Elk phosphorylation was completely blocked by dominant-negative Rho, Y27632, PP1, and latrunculin B, indicating that the Rho/ROCK pathway, Src kinase, and the actin cytoskeleton were required in this process. In accordance, neither nuclear ERK phosphorylation nor Elk phosphorylation were observed in SYF cells stimulated with SDF-1 but were reconstituted in Src ϩϩ cells. In summary, these results demonstrate that Src, Rho/ROCK, and an intact cytoskeleton contribute to overall ERK1/2 activation in SDF-1-stimulated cells and are indispensable for nuclear translocation of ERK1/2 and activation of transcription factors.

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mentioning

confidence: 55%

Regulation of CXCR4-Mediated Nuclear Translocation of Extracellular Signal-Related Kinases 1 and 2

et al. 2005

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“…Several lines of evidence indicate that CXCL12 induces endothelial cell migration, proliferation, tube formation and increases in VEGF release by endothelial cells [99][100][101]. Blockade of CXCL12/CXCR4 results in decreased tumor growth in vivo due to inhibition of angiogenesis in a VEGF-independent manner [102].…”

Section: Chemokines In Angiogenesismentioning

confidence: 99%

Chemokines in tumor angiogenesis and metastasis

Singh

Sadanandam

Singh

2007

Cancer Metastasis Rev

158

132

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Chemokines are a large group of low molecular weight cytokines that are known to selectively attract and activate different cell types. Although the primary function of chemokines is well recognized as leukocyte attractants, recent evidences indicate that they also play a role in number of tumor-related processes, such as growth, angiogenesis and metastasis. Chemokines activate cells through cell surface seven trans-membranes, G-protein-coupled receptors (GPCR). The role played by chemokines and their receptors in tumor pathophysiology is complex as some chemokines favor tumor growth and metastasis, while others may enhance anti-tumor immunity. These diverse functions of chemokines establish them as key mediators between the tumor cells and their microenvironment and play critical role in tumor progression and metastasis. In this review, we present some of the recent advances in chemokine research with special emphasis on its role in tumor angiogenesis and metastasis.

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“…The CXCL12-CXCR4 axis contributes to invasion and specific organ metastasis through regulation of its target genes, which have recently been shown to be VEGF and MMPs [7,16,25,26] . Therefore, we detected the effect of AMD3100 on expression of VEGF, MMP-2 and MMP-9.…”

Section: Effect Of Amd3100 On Expression Of Mmp-2 Mmp-9 and Vegf In mentioning

confidence: 99%

Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro

Lan²,

Shen³

et al. 2008

WJG

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Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro. World J Gastroenterol 2008; 14(15): 2308-2313 Available from: URL: http://www.wjgnet. com/1007-9327/14/2308.asp DOI: http://dx.doi.org/10.3748/ wjg.14.2308 INTRODUCTIONStromal cell-derived factor-1 (SDF-1 or CXCL12) and its unique receptor CXC chemokine receptor-4 (CXCR4) have prominent roles in invasion and metastasis of a diverse number of cancers. The interaction between SDF-1 and CXCR4 has been shown to direct tumor cells to organ sites with high levels of SDF-1 expression, which suggests this molecular pair plays a key role in chemotaxis and homing of metastatic cells. Convincing evidence indicates elevated CXCR4 expression in primary tumors is associated with lymph node metastasis in breasts [1][2][3][4] , head and neck [5] , and colon [6] . Furthermore, CXCR4 expression is associated with intraperitoneal carcinomatosis of ovarian [7] and gastric [8] cancer. High or persistent expression of CXCR4 has been associated with poor prognosis in osteosarcoma [9] , epithelial ovarian cancer [10] , colon cancer [6,11,12] , esophageal carcinoma [13] , and melanoma [14] . Recently, intensive research has shown that binding of CXCL12 to CXCR4 plays a role in tumor angiogenesis by influencing the secretion of vascular endothelial growth factor (VEGF) [15] and increasing invasion associated with matrix metalloproteinase (MMP)-9 activation [16] . Therefore, interruption of the interaction between CXCR4 and SDF-1 has received considerable attention since it may provide a means of inhibiting the metastatic process. AMD3100, a bicyclam molecule, has been identified as a specific inhibitor of CXCR4. It had originally been developed as an inhibitor of T-tropic human Abstract AIM: To investigate the effect and mechanism of blockade of the CXC chemokine receptor-4 (CXCR4) signaling pathway by AMD3100, a small non-peptide CXCR4 inhibitor, on invasion and metastasis of colorectal cancer cells in vitro .

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Stromal cell‐derived factor 1α (SDF‐1α) induces gene‐expression of early growth response‐1 (Egr‐1) and VEGF in human arterial endothelial cells and enhances VEGF induced cell proliferation

Cited by 72 publications

References 53 publications

Regulation of CXCR4-Mediated Nuclear Translocation of Extracellular Signal-Related Kinases 1 and 2

Regulation of CXCR4-Mediated Nuclear Translocation of Extracellular Signal-Related Kinases 1 and 2

Chemokines in tumor angiogenesis and metastasis

Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro

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