Inhibition of Angiogenesis by Somatostatin and Somatostatin-like Compounds Is Structurally Dependent

Barrie, Rosemary; Woltering, Eugene A.; Hajarizadeh, Homayon; Mueller, Charles R.; Ure, Tina; Fletcher, William S.

doi:10.1006/jsre.1993.1167

Cited by 92 publications

(44 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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: 73%

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

Vitali

Cambiaghi

Zerbi

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 73%

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

Vitali

Cambiaghi

Zerbi

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Besides the direct actions on pituitary cells, SRIF and its analogs also have indirect effects, since they inhibit production and secretion of many angiogenic factors, therefore reducing tumor growth rate (Barrie et al 1993). Neoangiogenesis is fundamental for tumor growth and one of the main factors promoting this process is vascular endotelial growth factor (VEGF).…”

Section: Page 9 Of 22mentioning

confidence: 99%

In vitro testing of new somatostatin analogs on pituitary tumor cells

Zatelli

Ambrosio

Bondanelli

et al. 2008

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

It has been indeed demonstrated that native SRIF inhibits secretion and proliferation of both normal and neoplasic pituitary cells by inducing several intracellular pathways, depending on receptor subtype and target tissue (Ferjoux et al. 2000). Therefore, many studies subsequently explored SSTR subtype expression in pituitary adenomas, demonstrating that SSTR2 is the most frequently expressed subtype (Panetta and Patel, 1995 A c c e p t e d M a n u s c r i p t 3 SSTR 2 and 5 mRNA were always expressed, while SSTR1 and 3 mRNA were expressed in 11 and 12 tumors, respectively. Primary cultures deriving from these tumors were tested with 1 M SRIF or lanreotide (Lan), a SRIF analog preferentially binding with high affinity SSTR2 and less affinity SSTR5, or with SSTR2-and SSTR5-selective analogs. After 24 hours no effect was observed in some cultures, but in others (as well as in the GH3 rat cell line) a parallel reduction in cell viability and DNA synthesis was observed. This study also highlighted a dissociation between the in vitro effects of SRIF analogs on tumor cell proliferation and on GH secretion. In nearly 60% of the tumors, treatment with SRIF, Lan, SSTR2-or SSTR5-selective agonists significantly inhibited GH secretion.by a median of 33%. However, not all these primary cultures responded to SRIF and its analogs in terms of cell viability reduction, suggesting that inhibition of cell proliferation occurs independently of the effects on GH secretion (Danila et al. 2001). Similarly, an important tumor shrinkage has been described in an acromegalic patient during primary therapy with SRIF analogs, in the absence of hormonal normalization . In this case, the lack of antisecretory action of octreotide, a SRIF analog preferentially binding with high affinity SSTR2 and less affinity SSTR5, was in keeping with the absence of SSTR2 and SSTR5 expression by the tumor, which expressed almost exclusively SSTR3. The latter SSTR subtype has been indeed demonstrated to transduce important antiproliferative signals, since its activation causes apoptosis in heterlogous expression systems (Sharma et al. 1996). Further support to the hypothesis that antiproliferative effects are independent of antisecretory actions of SRIF analogs is provided by a recent report, describing the case of an acromegalic patient displaying dramatic tumor shrinkage during primary therapy with octreotide, without hormonal normalization. Again, in vitro SRIF and its analogs at 10 nM induced a scant antisecretory effect, but potently inhibited thymidine incorporation. This effect was evident for compounds interacting with SSTR5, in keeping with the finding that SSTR5 expression levels were greater than SSTR2 in the tissue (Resmini et al. 2007). In light of the recent discoveries concerning SSTR biology, we attempted to clarify the possible functional interaction between SSTR and dopamine (DA) receptor subtype 2 (DR2). To this aim, we investigated DR2 and SSTR2 and 5 expression in 25 GH-secreting pituitary adenomas, which were tested in primary culture...

show abstract

“…The main mechanisms by which somatostatin analogues are thought to act in reducing bleeding include: platelet aggregation [39], decreased duodenal and splanchnic blood flow [40], increased vascular resistance [41], down-regulation of vascular endothelial growth factor (VEGF) expression [42] and inhibition of angiogenesis [42,43]. Somatostatin analogues have a better side-effect profile than other drugs such as anti-angiogenic drug [44,45] and hormonal treatment [46].…”

Section: Discussionmentioning

confidence: 99%

Refractory Anaemia Secondary to Small Bowel Angioectasias - Comparison between Endotherapy Alone versus Combination with Somatostatin Analogues

Zammit

Sidhu

Sanders

2017

JGLD

View full text Add to dashboard Cite

Background & Aims: Patients with small bowel angioectasias (SBAs) can be difficult to manage as they are generally elderly with multiple co-morbidities. Angioectasias are multiple and tend to recur. Argon plasma coagulation (APC), despite being a commonly used method to treat these patients has an associated persistent rate of re-bleeding necessitating additional treatment to manage these patients.Methods: All patients with refractory iron deficiency anaemia secondary to SBAs were retrospectively subdivided into two groups. Patients in group 1 were managed with double balloon enteroscopy (DBE) and APC alone and those in group 2 received Lanreotide in addition to DBE and APC.Results: A total of 49 patients were included in this study: group 1: 37 patients (75.5%), group 2: 12 patients (24.5%). All had significant comorbidities and the mean duration of anaemia was 114.3, SD 307.0 months. Significant improvements in haemoglobin (Hb) (11g/L vs 3.2g/L p=0.043), transfusion requirements per month (0.8 vs 4.7 p=0.052) and mean bleeding episodes (1.08 vs 2.6 p=0.032) were demonstrated in group 2 when compared to group 1. One patient developed symptomatic gallstone disease and one patient stopped Lanreotide due to a lack of response.Conclusions: This is the first study comparing endotherapy to a combination of endotherapy and pharmacotherapy. It shows a significantly better outcome in patients receiving a combination of endotherapy and Lanreotide. Lanreotide can be a safe additional treatment in patients not responding to APC alone.Abbreviations: APC: argon plasma coagulation; CE: capsule endoscopy; DBE double balloon enteroscopy; Hb: hemoglobin; OGIB: over gastrointestinal bleeding; SBAs: small bowel angioectasias.

show abstract

Inhibition of Angiogenesis by Somatostatin and Somatostatin-like Compounds Is Structurally Dependent

Cited by 92 publications

References 0 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

In vitro testing of new somatostatin analogs on pituitary tumor cells

Refractory Anaemia Secondary to Small Bowel Angioectasias - Comparison between Endotherapy Alone versus Combination with Somatostatin Analogues

Contact Info

Product

Resources

About