Role of the Ghrelin System in Colorectal Cancer

Abstract

The ghrelin system contains several components (e.g., ghrelin with growing number of alternative peptides, growth hormone secretagogue receptors (GHS-Rs), and ghrelin-O-acyl-transferase (GOAT) and participates in regulation of a number of key processes of gastrointestinal (GI) tract cancer progression, including cell proliferation, migration, invasion, apoptosis, inflammation, and angiogenesis. However, its exact role in promoting or inhibiting cancer progression is still unclear. Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Molecular studies suggest an autocrine/paracrine mechanism for the secretion of ghrelin in colorectal carcinogenesis and its contribution to its initial stages. However, the signalling pathways of CRC development involving the ghrelin system are poorly understood. Potential mechanisms of colon carcinogenesis involving components of the ghrelin system were previously described in an animal model and in in vitro studies. However, the diagnostic–prognostic role of serum ghrelin concentrations, tissue expression, or genetic changes of this system in various stages of CRC progression remains an open case. Thus, the aim of this study is to discuss the role of the ghrelin system in colon carcinogenesis, diagnostics and CRC prognostics, as well as the results of studies on the use of ghrelin and its analogues in the therapy of CRC-related syndromes (e.g., cachexia and sarcopenia).

Insights behind the Relationship between Colorectal Cancer and Obesity: Is Visceral Adipose Tissue the Missing Link?

“…Furthermore, it is thought that adipokines can have protumorigenic effects in the gastrointestinal tract; however, it is still not known whether they act directly on gastrointestinal mucosal cells or in an indirect, paracrine manner by inducing local inflammation [ 37 ]. In visceral obesity, a reduction in adipokines with anti-inflammatory and anticarcinogenic properties can lead to an increase in mitogenic signals, decreased cell apoptosis, and increased proangiogenic activity [ 43 ]. In the context of CRC, the most relevant adipocyte-secreted hormones are adiponectin, leptin, ghrelin, and resistin [ 37 ].…”

“…Ghrelin is an orexigenic peptide that acts as an important physiological regulator of lipid metabolism [ 43 ] and stimulates growth hormone release, adipogenesis, and changes the growth processes of neoplastic tissues, among other functions. It is known as the “hunger hormone” because of its stimulatory effect on food intake.…”

“…Interestingly, ghrelin may act as an antiapoptotic or proapoptotic factor in different cancer cells [ 37 ]. However, data are still inconsistent (reviewed extensively in [ 43 ]); even though a role for the ghrelin system in CRC pathogenesis has been described in vitro and animal studies, its relationship in human trials has been less conclusive. In this sense, some studies have shown that lower circulating ghrelin levels are associated with an increased risk of CRC, whereas others have reported no significant correlations or even an inverse correlation.…”

“…In this sense, some studies have shown that lower circulating ghrelin levels are associated with an increased risk of CRC, whereas others have reported no significant correlations or even an inverse correlation. Overall, it seems that most likely, reduced levels of ghrelin promote a metabolic proinflammatory environment that can be conducive to the development and growth of tumors in the context of CRC [ 43 ].…”

Role of the Ghrelin System in Colitis and Hepatitis as Risk Factors for Inflammatory-Related Cancers

“…The role of ghrelin system components in CRC itself was described in an earlier review [ 133 ]. Studies showing reduced ghrelin concentrations in CRC suggest a role for ghrelin in creating a metabolic proinflammatory environment in the early stages of CRC development, resulting in enhanced tumor growth.…”