Wnt2 acts as an angiogenic growth factor for non-sinusoidal endothelial cells and inhibits expression of stanniocalcin-1

Klein, Diana; Demory, Alexandra; Peyre, Francis; Krøll, Jens; Géraud, Cyrill; Ohnesorge, Nils; Schledzewski, Kai; Arnold, Bernd; Goerdt, Sergij

doi:10.1007/s10456-009-9145-5

Cited by 26 publications

(21 citation statements)

References 35 publications

(46 reference statements)

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“…[42][43][44][45][46] Furthermore, reduction of ␤-catenin correlates with EC apoptosis. 47,48 Our data are in accordance with earlier findings, which reported that Wnt/␤-catenin signaling is involved in the regulation of EC migration and cell cycle progression. 49 Based on our findings we have proposed a model through which sFRP4 interacts with the Wnt signaling pathway (Figure 6).…”

Section: Discussionsupporting

confidence: 83%

Secreted Frizzled-Related Protein 4

Muley

Majumder

Kolluru

et al. 2010

The American Journal of Pathology

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Wnt signaling is involved in developmental processes , cell proliferation , and cell migration. Secreted frizzled-related protein 4 (sFRP4) has been demonstrated to be a Wnt antagonist; however , its effects on endothelial cell migration and angiogenesis have not yet been reported. Using various in vitro assays, we show that sFRP4 inhibits endothelial cell migration and the development of sprouts and pseudopodia as well as disrupts the stability of endothelial rings in addition to inhibiting proliferation. sFRP4 interfered with endothelial cell functions by antagonizing the canonical Wnt/␤-catenin signaling pathway and the Wnt/planar cell polarity pathway. Furthermore, sFRP4 blocked the effect of vascular endothelial growth factor on endothelial cells. sFRP4 also selectively induced apoptotic events in endothelial cells by increasing cellular levels of reactive oxygen species. In vivo assays demonstrated a reduction in vascularity after sFRP4 treatment. Most importantly , sFRP4 restricted tumor growth in mice by interfering with endothelial cell function. The data demonstrate sFRP4 to be a potent angiogenesis inhibitor that warrants further investigation as a therapeutic agent in the control of angiogenesis-associated pathology.

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Section: Discussionsupporting

confidence: 83%

Secreted Frizzled-Related Protein 4

Muley

Majumder

Kolluru

et al. 2010

The American Journal of Pathology

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“…A number of studies have highlighted the possible involvement of STC1 in cellular apoptosis [Zhang et al, 2000;Wu et al, 2006;Law et al, 2008;Nguyen et al, 2009]. In addition to cell growth and apoptosis, STC1 was suggested to be a downstream target of VEGF/Wnt2 and was involved in angiogenic responses [Kahn et al, 2000;Wary et al, 2003;Zlot et al, 2003;Holmes and Zachary, 2008;Klein et al, 2009]. Retrospectively the literatures mirror the putative STC1 functions to the tumorigenic effects of Sp1-signalling.…”

Section: Discussionmentioning

confidence: 94%

Sp1 is a transcription repressor to stanniocalcin-1 expression in TSA-treated human colon cancer cells, HT29

et al. 2011

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Our previous study demonstrated that, stanniocalcin-1 (STC1) was a target of histone deacetylase (HDAC) inhibitors and was involved in trichostatin A (TSA) induced apoptosis in the human colon cancer cells, HT29. In this study, we reported that the transcriptional factor, specificity protein 1 (Sp1) in association with retinoblastoma (Rb) repressed STC1 gene transcription in TSA-treated HT29 cells. Our data demonstrated that, a co-treatment of the cells with TSA and Sp1 inhibitor, mithramycin A (MTM) led to a marked synergistic induction of STC1 transcript levels, STC1 promoter (1 kb)-driven luciferase activity and an increase of apoptotic cell population. The knockdown of Sp1 gene expression in TSA treated cells, revealed the repressor role of Sp1 in STC1 transcription. Using a protein phosphatase inhibitor okadaic acid (OKA), an increase of Sp1 hyperphosphorylation and so a reduction of its transcriptional activity, led to a significant induction of STC1 gene expression. Chromatin immunoprecipitation (ChIP) assay revealed that Sp1 binding on STC1 proximal promoter in TSA treated cells. The binding of Sp1 to STC1 promoter was abolished by the co-treatment of MTM or OKA in TSA-treated cells. Re-ChIP assay illustrated that Sp1-mediated inhibition of STC1 transcription was associated with the recruitment of another repressor molecule, Rb. Collectively our findings identify STC1 is a downstream target of Sp1.

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“…37.09.183G1050/09). Tumor induction was performed and collected as previously described (Klein et al 2009). In brief, for experimental tumor model, PC-3 cells (human prostate cancer cell line) were harvested by a brief trypsinization (0.05% trypsin/0.02% EDTA), washed, and resuspended in PBS at a density of 1 £ 10 7 cells/mL.…”

Section: Tissue and Cellsmentioning

confidence: 99%

Tumor vessel stabilization and remodeling by anti-angiogenic therapy with bevacizumab

Weißhardt

Trarbach

Dürig

et al. 2011

Histochem Cell Biol

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Bevacizumab-resistant tumor vessels were characterized by an increased vessel diameter and normalization of vascular structures by the recruitment of mature pericytes and smooth muscle cells. Here, we analyzed human liver metastases which were taken at clinical relapse in patients with colorectal adenocarcinoma treated with anti-angiogenic therapy using the humanized monoclonal anti-VEGF bevacizumab. Tumor vessels which are resistant to anti-VEGF therapy are increased in size and characterized by a normalization of the vascular bed. These results were confirmed using NOD SCID mice as animal model and xenograft transplantation of human PC-3 prostate carcinoma cells in combination with bevacizumab treatment. Our results confirmed that anti-angiogenic therapy results in enhanced vascular remodeling by vascular stabilization. This process is apparently accompanied by enhanced necrosis of tumor tissue. These processes interfere with the efficacy of anti-angiogenic therapy because of reduced susceptibility of stabilized vessels by this therapy. These results demonstrate the importance for the development of second generation anti-angiogenic combination therapy concepts to rule out the balance between vascular stabilization followed by a possible de-stabilization making the remained vessels susceptible to a second wave of anti-angiogenic therapy.

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Wnt2 acts as an angiogenic growth factor for non-sinusoidal endothelial cells and inhibits expression of stanniocalcin-1

Cited by 26 publications

References 35 publications

Secreted Frizzled-Related Protein 4

Secreted Frizzled-Related Protein 4

Sp1 is a transcription repressor to stanniocalcin-1 expression in TSA-treated human colon cancer cells, HT29

Tumor vessel stabilization and remodeling by anti-angiogenic therapy with bevacizumab

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