Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane

Woltering, Eugene A.; Barrie, Rosemary; O'Dorisio, Thomas M.; Arce, Dennis; Ure, Tina; Cramer, Andrew; Holmes, Douglas P.; Robertson, Joseph E.; Fassler, J.E.

doi:10.1016/0022-4804(91)90186-p

Cited by 103 publications

(52 citation statements)

References 14 publications

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“…In particular, it has been demonstrated that FLNA physically interacts with HIF-1a (Zhenga et al 2014), that regulates angiogenesis through upregulation of vascular endothelial growth factor (VEGF) (Uramoto et al 2010, Berardi et al 2011, Semenza 2012. Whereas VEGF-driven angiogenesis may play an important role in endocrine tumourigenesis and tumour progression (Hanahan et al 1996) and several in vitro studies suggested that SS analogues display potent antiangiogenic properties (Woltering et al 1991, Barrie et al 1993, Danesi & Del Tacca 1996, Kumar et al 2004, we showed that SST2 agonist reduced VEGF protein levels and release, but this inhibitory effect was totally abolished in the absence of FLNA.…”

Section: Discussionmentioning

confidence: 72%

Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

Vitali

Cambiaghi

Zerbi

et al. 2016

Endocrine-Related Cancer

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Somatostatin receptor type 2 (SST2) is the main pharmacological target of somatostatin (SS) analogues widely used in patients with pancreatic neuroendocrine tumours (P-NETs), this treatment being ineffective in a subset of patients. Since it has been demonstrated that Filamin A (FLNA) is involved in mediating GPCR expression, membrane anchoring and signalling, we investigated the role of this cytoskeleton protein in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in human P-NETs and in QGP1 cell line. We demonstrated that FLNA silencing was not able to affect SST2 expression in P-NET cells in basal conditions. Conversely, a significant reduction in SST2 expression (K43G21%, P!0.05 vs untreated cells) was observed in FLNA silenced QGP1 cells after long term SST2 activation with BIM23120. Moreover, the inhibitory effect of BIM23120 on cyclin D1 expression (K46G18%, P!0.05 vs untreated cells), P-ERK1/2 levels (K42G14%; P!0.05 vs untreated cells), cAMP accumulation (K24G3%, P!0.05 vs untreated cells), VEGF expression (K31G5%, P!0.01 vs untreated cells) and in vitro release (K40G24%, P!0.05 vs untreated cells) was completely lost after FLNA silencing. Interestingly, BIM23120 promoted cell adhesion (C86G45%, P!0.05 vs untreated cells) and inhibited cell migration (K24G2%, P!0.00001 vs untreated cells) in P-NETs cells and these effects were abolished in FLNA silenced cells. In conclusion, we demonstrated that FLNA plays a crucial role in SST2 expression and signalling, angiogenesis, cell adhesion and cell migration in P-NETs and in QGP1 cell line, suggesting a possible role of FLNA in determining the different responsiveness to SS analogues observed in P-NET patients.

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Section: Discussionmentioning

confidence: 72%

Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

Vitali

Cambiaghi

Zerbi

et al. 2016

Endocrine-Related Cancer

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“…Indeed, treatment with SRIF and pasireotide completely abrogates the growth-promoting effects VEGF on NFA primary cultures. In addition, it has been previously reported that octreotide reduces blood vessel growth (Woltering et al 1991) and inhibits proliferation of human umbilical vein endothelial cells (Danesi et al 1997). Our data also indicate that VEGF might promote pituitary proliferation both indirectly, by stimulating angiogenesis, and directly by promoting cell viability.…”

Section: Discussionmentioning

confidence: 99%

Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

Zatelli¹,

Piccin²,

Tagliati³

et al. 2007

Endocr Relat Cancer

108

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“…Experimental angiogenesis has been inhibited by the synthetic sst analogue Octreotide (Woltering et al, 1991;Danesi and Del Tacca, 1996;Danesi et al, 1997) that has a high affinity for sst 2. Human umbilical vein endothelial cells (HUVECs), which are widely used as an endothelial cell model in vitro, have also been shown to express sst 2 (Curtis et al, 2000).…”

mentioning

confidence: 99%

Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium

Adams

Lindow

et al. 2005

Br J Cancer

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Angiogenesis is characterised by activation, migration and proliferation of endothelial cells and is central to the pathology of cancer, cardiovascular disease and chronic inflammation. Somatostatin is an inhibitory polypeptide that acts through five receptors (sst 1, 2, 3, 4, 5). Sst has previously been reported in endothelium, but their role remains obscure. Here, we report the expression of sst in human umbilical vein endothelial cells (HUVECs) in vitro, during proliferation and quiescence. A protocol for culturing proliferating and quiescent HUVECs was established, and verified by analysing cell cycle distribution in propidium-iodide-stained samples using flow cytometry. Sst mRNA was then quantified in nine proliferating and quiescent HUVEC lines using quantitative reverse transcriptase -polymerase chain reaction. Sst 2 and 5 were preferentially expressed in proliferating HUVECs. All samples were negative for sst 4. Sst 1 and 3 expression and cell cycle progression were unrelated. Immunostaining for sst 2 and 5 showed positivity in proliferating but not quiescent cells, confirming sst 2 and 5 protein expression. Inhibition of proliferating cells with somatostatin analogues Octreotide and SOM230, which have sst 5 activity, was found (Octreotide 10 À10 -10 À6 M: 48.5 -70.2% inhibition; SOM230 10 À9 -10 À6 M: 44.9 -65.4% inhibition) in a dose-dependent manner, suggesting that sst 5 may have functional activity in proliferation. Dynamic changes in sst 2 and 5 expression during the cell cycle and the inhibition of proliferation with specific analogues suggest that these receptors may have a role in angiogenesis.

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Somatostatin analogues inhibit angiogenesis in the chick chorioallantoic membrane

Cited by 103 publications

References 14 publications

Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

Filamin-A is required to mediate SST2 effects in pancreatic neuroendocrine tumours

Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium

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