A role of ghrelin in cancerogenesis

Majchrzak, Kinga; Szyszko, K.; Pawłowski, Krzysztof; Motyl, T.; Król, Magdalena

doi:10.2478/v10181-011-0133-5

Cited by 19 publications

(23 citation statements)

References 56 publications

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“…Ghrelin signaling has increasingly been recognized as a key regulator of obesity, insulin resistance and diabetes; intriguingly, many of these regulatory functions appear to be independent of ghrelin's effect on food intake (4–8). This current review is focused on the most recent findings of ghrelin in glucose homeostasis (9–11), energy-homeostasis (7, 12), heart disease (13–16), muscular atrophy (17, 18), bone metabolism (8, 19, 20), and cancer development/progression (21, 22). …”

Section: Introductionmentioning

confidence: 99%

“…Ghrelin and GHS-R have been detected in many endocrine and non-endocrine tumors (21, 22), suggesting that the ghrelin/GHS-R axis might be associated with tumor growth and progression. In pituitary tumors, ghrelin mRNA is detected in non-functional adenomas, GH- and gonadotropin-producing adenomas and prolactinomas, with highest GHS-R expression detected in the GH-producing adenomas (51).…”

Section: Introductionmentioning

confidence: 99%

“…Various studies have reported that ghrelin exhibits proliferative properties in cancer (21). A recent study in canine mammary carcinoma shows high levels of ghrelin and GHS-R in metastatic tumors (22).…”

Section: Introductionmentioning

confidence: 99%

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Ghrelin

Pradhan¹,

Samson²,

Sun³

2013

Current Opinion in Clinical Nutrition and Metabolic Care

246

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Purpose of review Ghrelin is a multifaceted gut hormone which activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on food intake, fat deposition and growth hormone release. Ghrelin is famously known as the “hunger hormone”. However, ample literature indicates that the functions of ghrelin go well beyond its role as an orexigenic signal. Here we have reviewed some of the most recent findings on ghrelin and its signaling in animals and humans. Recent findings Ghrelin regulates glucose hemostasis by inhibiting insulin secretion and regulating gluconeogenesis/glycogenolysis. Ghrelin signaling decreases thermogenesis to regulate energy expenditure. Ghrelin improves the survival prognosis of myocardial infarction by reducing sympathetic nerve activity. Ghrelin prevents muscle atrophy by inducing muscle differentiation and fusion. Ghrelin regulates bone formation and metabolism by modulating proliferation and differentiation of osteoblasts. Ghrelin is also involved in cancer development and metastasis; ghrelin and GHS-R mRNA are highly expressed in metastatic forms of cancers. Summary In addition to ghrelin's effects on appetite and adiposity, ghrelin signaling also plays crucial roles in glucose- and energy-homeostasis, cardioprotection, muscle atrophy, bone metabolism and cancer. These multifaceted roles of ghrelin make ghrelin and GHS-R highly attractive targets for drug development.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ghrelin

Pradhan¹,

Samson²,

Sun³

2013

Current Opinion in Clinical Nutrition and Metabolic Care

246

View full text Add to dashboard Cite

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“…The co-expression of ghrelin and GHS-R has previously been observed in various neoplasms and related cancer cell lines in humans (for review see: [10]). It may suggest their role in neoplastic cell growth and development through autocrine/paracrine mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…The ghrelin expression (and its receptor) has also been observed in multiple endocrine and non-endocrine tumors and related cell lines in humans, such as: pituitary adenomas, thyroid follicular cancer and parathyroid adenomas, pancreatic-related endocrine tumors, oral squamous cell carcinoma, gastric carcinoids, colon cancer, renal carcinoma, bronchial carcinoid, testicular and ovarian tumors, adrenocortical tumors, prostate cancer and breast cancer [10]. The co-expression of ghrelin and its receptor in various tumors and cancer cell lines may indicate their autocrine/paracrine role in the tumor growth and development.…”

Section: Introductionmentioning

confidence: 99%

A role of ghrelin in canine mammary carcinoma cells proliferation, apoptosis and migration

et al. 2012

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BackgroundGhrelin is a natural ligand of the growth hormone secretagogue receptor (GHS-R). They are often co-expressed in multiple human tumors and related cancer cell lines what can indicate that the ghrelin/GHS-R axis may have an important role in tumor growth and progression. However, a role of ghrelin in canine tumors remains unknown. Thus, the aim of our study was two-fold: (1) to assess expression of ghrelin and its receptor in canine mammary cancer and (2) to examine the effect of ghrelin on carcinoma cells proliferation, apoptosis, migration and invasion. The expression of ghrelin and its receptor in canine mammary cancer tissues and cell lines (isolated from primary tumors and their metastases) was examined using Real-time qPCR and immunohistochemistry. For apoptosis analysis the Annexin V and propidium iodide dual staining was applied whereas cell proliferation was evaluated by MTT assay and BrdU incorporation test. The influence of ghrelin on cancer cells migration and invasion was assessed using Boyden chamber assays and wound healing assay.ResultsThe highest expression of ghrelin was observed in metastatic cancers whereas the lowest expression of ghrelin receptor was detected in tumors of the 3rd grade of malignancy. Higher expression of ghrelin and its receptor was detected in cancer cell lines isolated from metastases than in cell lines isolated from primary tumors. In vitro experiments demonstrated that exposure to low doses of ghrelin stimulates cellular proliferation, inhibits apoptosis and promotes motility and invasion of canine mammary cancer cells. Growth hormone secretagogue receptor inhibitor ([D-Lys3]-GHRP6) as well as RNA interference enhances early apoptosis.ConclusionThe presence of ghrelin and GHS-R in all of the examined canine mammary tumors may indicate their biological role in cancer growth and development. Our experiments conducted in vitro confirmed that ghrelin promotes cancer development and metastasis.

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