Peptide Receptor Targeting in Cancer: The Somatostatin Paradigm

Abstract

Peptide receptors involved in pathophysiological processes represent promising therapeutic targets. Neuropeptide somatostatin (SST) is produced by specialized cells in a large number of human organs and tissues. SST primarily acts as inhibitor of endocrine and exocrine secretion via the activation of five G-protein-coupled receptors, named sst1–5, while in central nervous system, SST acts as a neurotransmitter/neuromodulator, regulating locomotory and cognitive functions. Critical points of SST/SST receptor biology, such as signaling pathways of individual receptor subtypes, homo- and heterodimerization, trafficking, and cross-talk with growth factor receptors, have been extensively studied, although functions associated with several pathological conditions, including cancer, are still not completely unraveled. Importantly, SST exerts antiproliferative and antiangiogenic effects on cancer cells in vitro, and on experimental tumors in vivo. Moreover, SST agonists are clinically effective as antitumor agents for pituitary adenomas and gastro-pancreatic neuroendocrine tumors. However, SST receptors being expressed by tumor cells of various tumor histotypes, their pharmacological use is potentially extendible to other cancer types, although to date no significant results have been obtained. In this paper the most recent findings on the expression and functional roles of SST and SST receptors in tumor cells are discussed.

68Ga DOTATATE Uptake in Vertebral Hemangioma

“…8 We assume that 68 Ga DOTATATE binds to endothelial cells, which are known to express SSTR2 receptors, whereas adipocytes do not. There is also the possibility of binding to circulating blood cells (eg, lymphocytes, monocytes, and macrophages), 9 although we believe that this could only lead to a weak degree of uptake. The reported case provides a further benign differential diagnosis when evaluating somatostatin receptor scintigraphies and demonstrates the advantage of hybrid imaging modalities such as PET/CT or PET/MRI for obtaining conclusive tumor staging information in a single setting.…”

Immuno-histomorphometric and -fluorescent characteristics of GH cells after treatment with genistein or daidzein in an animal model of andropause

“…Literature data indicate the possible alterations in somatostatin receptors (SSTRs) expression after genistein application in vitro, as a matter of fact the SSTR1 downregulation, as well as the SSTR2 and SSTR5 upregulation [25]. Considering that an alternative SSTR expression in pituitary GH secreting tumors causes the insensitivity to somatostatin [26], it seems logical that some soy isofl avone modifi ed SSTR expression in GH cells may have a related outcome responsible for Somatopauza, kao kompleksan aspekt andropauze, je prepoznatljiva po sniženom nivou funkcije somatotropne -GH ose kod starih mužjaka. Izofl avoni soje (najčešće genistein i daidzein), imaju blagotvorne efekte pri tretmanu simptoma starenja, a ispoljavaju svoje dejstvo i na nivou hipofi ze.…”

Somatostatin receptor expression in hepatocellular carcinoma: prognostic and therapeutic considerations

“…1B) and apoptosis ( Fig. 1C) (Lamberts et al 1996, Dasgupta 2004, Barbieri et al 2013). An anti-angiogenic effect of SST and SSAs has also been described, which seems to be related to paracrine inhibition …”

“…All SSTRs have capability to bind natural SST14 and SST28 with a high affinity, while there is a significant variation in binding of synthetic SST peptides or somatostatin analogues (SSAs) (Barbieri et al 2013) (see Table 1). …”