The use of suppression subtractive hybridization for the study of SDF-1α induced gene-expression in human endothelial cells

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

doi:10.1016/j.mcp.2003.07.007

Cited by 4 publications

(4 citation statements)

References 57 publications

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“…SDF-1 acts as a chemoattractant for endothelial cells and their progenitors, induces endothelial cell proliferation in vitro, enhances VEGF-induced proliferation of endothelial cells, and induces microvessel formation and capillary sprouting in vivo. 44,53,54 In addition, an angiogenic role of SDF-1 has been shown at sites of inflammation, 53 wound repair 55 and in gliomas. 31 It has been proposed that the chemotactic influence of SDF-1a 44,56 combined with the proliferative effects of VEGF may represent a powerful angiogenic signal.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion

Zagzag

Lukyanov

Lan

et al. 2006

Laboratory Investigation

348

290

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Hypoxia and hypoxia-inducible factor-1 (HIF-1) play a critical role in glioblastoma multiforme (GBMs). CXCR4 is involved in angiogenesis and is upregulated by HIF-1alpha. CXCR4 is a chemokine receptor for stromal cell-derived factor-1 (SDF-1)alpha, also known as CXCL12. We hypothesized that CXCR4 would be upregulated by hypoxia in GBMs. First, we investigated the expression of HIF-1alpha and CXCR4 in GBMs. CXCR4 was consistently found colocalized with HIF-1alpha expression in pseudopalisading glioma cells around areas of necrosis. In addition, angiogenic tumor vessels were strongly positive for CXCR4. Next, we tested the in vitro effect of hypoxia and vascular endothelial growth factor (VEGF) on the expression of CXCR4 in glioma cell lines and in human brain microvascular endothelial cells (HBMECs). Exposure to hypoxia induced significant expression of CXCR4 and HIF-1alpha in glioma cells, whereas treatment with exogenous VEGF increased CXCR4 expression in HBMECs. We also transfected U87MG glioma cells with an HIF-1alpha construct and observed that CXCR4 was upregulated in these cells even in normoxic conditions. We then used a lentivirus-mediated shRNA expression vector directed against HIF-1alpha. When exposed to hypoxia, infected cells failed to show HIF-1alpha and CXCR4 upregulation. We performed migration assays under normoxic and hypoxic conditions in the presence or absence of AMD3100, a CXCR4 inhibitor. There was a significant increase in the migration of U87MG and LN308 glioma cells in hypoxic conditions, which was inhibited in the presence of AMD3100. These studies demonstrate the critical role played by hypoxia and CXCR4 in glioma cell migration. Based on these studies, we suggest that hypoxia regulates CXCR4 in GBMs at two levels. First, through HIF-1alpha in the pseudopalisading tumor cells themselves and, secondly, by the VEGF-stimulated angiogenic response in HBMECs. We believe this knowledge may lead to a potentially important two-pronged therapy against GBM progression using chemotherapy targeting CXCR4.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion

Zagzag

Lukyanov

Lan

et al. 2006

Laboratory Investigation

348

290

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“…SDF-1a increases VEGF expression and enhances VEGF-induced proliferation of endothelial cells (48,49). In addition, both VEGF and SDF-1a up-regulate EGR-1, a transcription factor that upregulates expression of VEGF-receptor Flt-1 (50).…”

Section: Discussionmentioning

confidence: 99%

Stromal Cell–Derived Factor-1α and CXCR4 Expression in Hemangioblastoma and Clear Cell-Renal Cell Carcinoma: von Hippel-Lindau Loss-of-Function Induces Expression of a Ligand and Its Receptor

et al. 2005

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“…This then results in neo-angiogenesis and tissue regeneration by homing of stem cells and endothelial progenitor cells to the site of ischemic injury e.g., after infarction in the heart (Abbott et al, 2004;Askari et al, 2003;Burger and Kipps 2006;De Falco et al,2004). Also, SDF-1 modulates expression of thymosin b4, a peptide shown to affect cardiomyocyte survival, migration and repair via the survival kinase Akt (Bock-Marquette et al, 2004;Neuhaus et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Early postnatal lethality and cardiovascular defects in CXCR7‐deficient mice

Gerrits

Schenau²,

Bakker

et al. 2008

Genesis

126

127

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CXCR7 is a G-protein coupled receptor that was recently deorphanized and shown to have SDF1 and I-TAC as high affinity ligands. Here we describe the characterization of CXCR7-deficient mice that were generated to further investigate the function of this receptor in vivo. Expression analysis using a LacZ reporter knockin revealed that postnatally Cxcr7 was specifically expressed in cardiomyocytes, vascular endothelial cells of the lung and heart, the cerebral cortex and in osteocytes of the bone. Adult tissues revealed high expression in cardiomyocytes and osteocytes. The observation that 70% of the Cxcr7-/- mice died in the first week after birth coincides with expression of Cxcr7 in vascular endothelial cells and in cardiomyocytes. An important role of CXCR7 in the cardiovascular system was further supported by the observation that hearts of the Cxcr7-/- mice were enlarged, showed myocardial degeneration and fibrosis of postnatal origin, and hyperplasia of embryonic origin. Despite high expression in osteocytes no apparent bone phenotype was observed, neither in combination with ovariectomy nor orchidectomy. Thus as CXCR7 does not seem to play an important role in bone our data indicate an important function of CXCR7 in the cardiovascular system during multiple steps of development.

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The use of suppression subtractive hybridization for the study of SDF-1α induced gene-expression in human endothelial cells

Cited by 4 publications

References 57 publications

Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion

Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion

Stromal Cell–Derived Factor-1α and CXCR4 Expression in Hemangioblastoma and Clear Cell-Renal Cell Carcinoma: von Hippel-Lindau Loss-of-Function Induces Expression of a Ligand and Its Receptor

Early postnatal lethality and cardiovascular defects in CXCR7‐deficient mice

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