cortistatin-14 and Neoplasms

Somatostatin receptors (sst), somatostatin (SS) and cortistatin (CST) are widely expressed in the various systems in the human and rodent organisms and are "responsible" for maintaining homeostasis, which is essential for survival. Because of their broad expression pattern sst, SS and CST interactions may play regulatory roles in both physiology and pathophysiology in mammalian organisms. SS analogue treatment strategies as well as the use of SS analogues for diagnostic purposes have been established in diseases of different origins. This review focuses on the currently determined role for SS analogues in today's clinical practice and the potential clinical prospects for SS, CST and sst interactions in the future, with a focus on neuroendocrine and non-neuroendocrine tumours and immune-mediated diseases. Moreover, the role of new SS analogues and new insights in sst physiology will be discussed.

Topics: Antineoplastic Agents, Hormonal; Endocrine Gland Neoplasms; Endocrine System Diseases; Humans; Immune System; Immune System Diseases; Neoplasms; Neuropeptides; Neurosecretory Systems; Radionuclide Imaging; Receptors, Somatostatin; Somatostatin

Somatostatin (SS) and its synthetic analogs have a role in the treatment of neuroendocrine tumours both in terms of symptoms control and antiproliferative activities. These effects are mediated by five SS receptors, widely expressed in both human neuroendocrine and non-neuroendocrine tumours, which were demonstrated to be diagnostically and therapeutically valuable targets. Cortistatin (CST), a brain cortex peptide, partially homologous to SS and having similar functions is also expressed in peripheral tissues and tumours. CST binds all SS receptors, and, differently from SS, also the ghrelin receptor GHSR1a and the CST specific receptor MrgX2. The expression profile of CST is mostly restricted to neuroendocrine tumours (gastrointestinal, pancreas, lung, parathyroid, thyroid, adrenal). In these tumours, CST probably acts via the SS or ghrelin receptor, the MrgX2 receptor being absent. Thus, in comparison to SS analogs, CST synthetic analogs may represent additional diagnostic/therapeutic tools in those tumours expressing the receptors for SS, for ghrelin or for both peptides.

Topics: Binding, Competitive; Humans; Neoplasms; Nerve Tissue Proteins; Neuroendocrine Tumors; Neuropeptides; Neurosecretory Systems; Receptors, G-Protein-Coupled; Receptors, Ghrelin; Receptors, Neuropeptide; Receptors, Somatostatin; Somatostatin

Cortistatin (CST) is a neuropeptide that strongly resembles somatostatin (SS) structurally and functionally. CST binds to all five SS receptors (SSTR1-SSTR5) with high affinity and exerts its function mainly through SSTRs. Despite many similar functions between these two neuropeptides, they are products of different genes. Recently, some distinct functions and receptor usage of CST have been reported. Some of the interesting functions of CST were not found with SS. Therefore CST could have potential new roles in an ex-neuronal system that regulates immune responses as well as other cellular functions in the body. In this review, we discuss the new functions of CST in the immune system, cancer pathogenesis, and possible CST-specific receptors.

Topics: Endothelial Cells; Humans; Neoplasms; Neuropeptides; Receptors, Neuropeptide

Somatostatin and cortistatin, a recently discovered endogenous neuropeptide relative of somatostatin, have multiple modulatory effects on the immune system. The specific somatostatin receptor distribution might in part explain the heterogeneity of effects of somatostatin or its analogs on immunocytes. In fact, somatostatin receptor subtypes are differentially expressed on specific cell subsets within the organs of the immune system and the expression is dynamically regulated and seems to depend on the traffic of these cells through and within lymphoid structure and homing in tissues. Somatostatin effects on immune cells are mainly based on autocrine and paracrine modes of action. In fact, activated cells producing somatostatin (or cortistatin) may interact with other cells expressing the receptors. Here, we review the postulated modes of action of somatostatin and somatostatin-like peptides, including the currently available synthetic somatostatin analogs, in cells of the immune system. We also discuss the wide distribution of somatostatin and its specific five receptor subtypes in immune cell lines, as well as throughout animal and human lymphoid organs, in both normal and pathological conditions.

Topics: Animals; Autoimmune Diseases; Granulomatous Disease, Chronic; Humans; Immune System; Neoplasms; Neuropeptides; Rats; Receptors, Somatostatin; Somatostatin; Tissue Distribution

Cancer is responsible for millions of deaths throughout the world every year. Increased understanding as well as advancements in the therapeutic aspect seems suboptimal to restrict the huge deaths associated with cancer. The major cause responsible for this is high resistance as well as relapse rate associated with cancers. Several evidences indicated that cancer stem cells (CSC) are mainly responsible for the resistance and relapses associated with cancer. Furthermore, agents targeting a single protein seem to have higher chances of resistance than multitargeting drugs. According to the concept of network model, partial inhibition of multiple targets is more productive than single hit agents. Thus, by fusing both the premises that CSC and single hit anticancer drugs, both are responsible for cancer related resistances and screened alkaloids for the search of leads having CSC targeting ability as well as the capability to modulating multiple target proteins. The in silico experimental data indicated that emetine and cortistatin have the ability to modulate hedgehog (Hh) pathway by binding to sonic hedgehog (Hh), smoothened (Smo) and Gli protein, involved in maintenance CSCs. Furthermore, solamargine, solasonine and tylophorine are also seems to be good lead molecules targeting towards CSCs by modulating Hh pathway. Except solamargine and solasonine, other best lead molecules also showed acceptable in silico ADME profile. The predicted lead molecules can be suitably modified to get multitargeting CSC targeting agent to get rid of associate resistances.

Topics: Alkaloids; Antineoplastic Agents; Cell- and Tissue-Based Therapy; Drug Delivery Systems; Drug Screening Assays, Antitumor; Emetine; Hedgehog Proteins; Humans; Models, Molecular; Molecular Docking Simulation; Neoplasms; Neoplastic Stem Cells; Neuropeptides; Signal Transduction