Abstract
Somatostatin (SST)/somatotropin release-inhibiting factor (SRIF) is a well-known neuropeptide, widely distributed in the central and peripheral nervous systems, that regulates the endocrine system and affects neurotransmission via interaction with five SST receptors (SST1-5). In the gastrointestinal tract, the main SST-producing cells include intestinal enteroendocrine cells (EECs) restricted to the mucosa, and neurons of the submucosal and myenteric plexuses. The action of the SRIF system is based on the inhibition of endocrine and exocrine secretion, as well as the proliferative responses of target cells. The SST1–5 share common signaling pathways, and are not only widely expressed on normal tissues, but also frequently overexpressed by several tumors, particularly neuroendocrine neoplasms (NENs). Furthermore, the SRIF system represents the only peptide/G protein-coupled receptor (GPCR) system with multiple approved clinical applications for the diagnosis and treatment of several NENs. The role of the SRIF system in the histogenesis of colorectal cancer (CRC) subtypes (e.g., adenocarcinoma and signet ring-cell carcinoma), as well as diagnosis and prognosis of mixed adenoneuroendocrine carcinoma (MANEC) and pure adenocarcinoma, is poorly understood. Moreover, the impact of the SRIF system signaling on CRC cell proliferation and its potential role in the progression of this cancer remains unknown. Therefore, this review summarizes the recent collective knowledge and understanding of the clinical significance of the SRIF system signaling in CRC, aiming to evaluate the potential role of its components in CRC histogenesis, diagnosis, and potential therapy.
Highlights
(2 cm wide) surrounding the human colorectal cancer (CRC), as compared with veins located at a greater distance (5–10 cm) in control tissue. These results suggest the presence of a regulatory mechanism in the tumor vascular bed, which could be key for the development of CRC
The lack of SST and SST receptor type 1 (SST1) expression on ALDH(+) stem cells suggested that SST signaling controls the maturation rate of neuroendocrine cells (NCs), as SCs mature into the NC lineage, which contributes to silencing of SCs and inhibition of proliferation
In the GI tract, most studies have investigated the role of somatotropin release-inhibiting factor (SRIF) system in the physiology and pathology of various neuroendocrine neoplasms (NENs)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In peripheral tissues, mostly the gastrointestinal (GI) tract, it serves as a pan-inhibitory peptide in processes of endocrine and exocrine secretion It affects the motility, blood flow, and intestinal absorption, and exhibits anti-inflammatory activities [13,14,15]. The SRIF system is characterized by a strong antiproliferative activity, increasing cell apoptosis and inhibiting angiogenesis in most of the cancerous tissues [12,16,17,18,19,20] This property is already used in clinical practice [20,21,22,23,24,25,26]. This review summarizes the recent collective knowledge and understanding of the clinical significance of the SRIF system signaling in colorectal cancer, aiming to evaluate the potential role of this system’s components in CRC histogenesis, diagnosis and potential therapy
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