Ghrelin: A potential therapeutic target for cancer

Regulatory Peptides

Volumn 163, Issue 1-3, 2010, Pages 7-17

  Nikolopoulos, Dimitrios ^a   Theocharis, Stamatis ^a   Kouraklis, Gregory ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

Author keywords

Cancer; Ghrelin; Ghrelin receptor; Growth hormone secretagogues (GHSs)

Indexed keywords

AMINO ACID; GHRELIN; GHRELIN RECEPTOR; GROWTH HORMONE; GROWTH HORMONE SECRETAGOGUE RECEPTOR;

AUTOCRINE EFFECT; CANCER TISSUE; CARDIOVASCULAR SYSTEM; CELL PROLIFERATION; DRUG TARGETING; FOOD INTAKE; GASTROINTESTINAL TRACT; GENE EXPRESSION; GROWTH HORMONE RELEASE; HORMONE RELEASE; HUMAN; IMMUNE SYSTEM; MAMMAL; NEOPLASM; NONHUMAN; PARACRINE SIGNALING; PRIORITY JOURNAL; PROGNOSIS; RESPIRATORY SYSTEM; REVIEW; STOMACH MUCOSA;

ANIMALS; GHRELIN; HUMANS; NEOPLASMS; RECEPTORS, GHRELIN;

MAMMALIA;

EID: 77953962353     PISSN: 01670115     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.regpep.2010.03.011     Document Type: Review

References (92)

1. Bowers C.Y., Momany F., Reynolds G.A., Chang D., Hong A., Chang K. Structure-activity relationships of a synthetic pentapeptide that specifically releases growth hormone in vitro. Endocrinology 1980, 106:663-667.
2. Pandol S.J., Seifert H., Thomas M.W., Rivier J., Vale W. Growth hormone-releasing factor stimulates pancreatic enzyme secretion. Science 1984, 225(4659):326-328.
3. Dickson S.L., Leng G., Dyball R.E., Smith R.G. Central actions of peptide and non-peptide growth hormone secretagogues in the rat. Neuroendocrinology 1995, 61(1):36-43.
4. Laron Z. Growth hormone secretagogues. Clinical experience and therapeutic potential. Drugs 1995, 50(4):595-601.
5. Smith R.G., Palyha O.C., Feighner S.D. Growth hormone releasing substances: types and their receptors. Horm Res 1999, 51:1-8.
6. Kojima M., Hosoda H., Date Y., Nakazato Masamitsu, Matsuo Hisayuki, Kangawa Kenji Ghrelin is a growth hormone releasing acylated peptide from stomach. Nature 1999, 402:656-660.
7. Hosoda H., Kojima M., Matsuo H., Kangawa K. Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 2000, 279:909-913.
8. Kojima M., Hosoda H., Matsuo H., Kangawa K. Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab 2001, 3:118-122.
9. Takada R., Satomi Y., Kurata T., Ueno N., Norioka S., Kondoh H., Takao T., Takada S. Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Dev Cell 2006, 11(6):791-801.
10. Yang J., Brown M.S., Liang G., Grishin N., Goldstein L. Identification of the Acyltransferase that octanoylates Ghrelin, an appetite-stimulating peptide hormone. Cell 2008, 132:387-396.
11. Gutierrez J.A., Solenberg P.J., Perkins D.R., Willency J.A., Knierman M.D., Jin Z., Witcher D.R., Luo S., Onyia J.E., Hale J.E. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci USA 2008, 105(17):6320-6325.
12. Banks W.A., Tschop M., Robinson S.M., Heiman M.L. Extent and direction of Ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther 2002, 302:822-827.
13. Bednarek M.A., Feighner S.D., Pong S.S., McKee K.K., Hreniuk D.L., Silva M.V., Warren V.A., Howard A.D., Van Der Ploeg L.H., Heck J.V. Structure and function studies on the new growth hormone releasing peptide, ghrelin: minimal sequence of Ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J Med Chem 2000, 43:4370-4376.
14. Kojima M., Kangawa K. Ghrelin: structure and function. Physiol Rev 2005, 85:495-522.
15. Broglio F., Benso A., Gottero C., Prodam F., Gauna C., Filtri L., Arvat E., van der Lely A.J., Deghenghi R., Ghigo E. Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin in humans. J Endocrinol Invest 2003, 26:192-196.
16. Alloatti B.G., Marcantoni A., Malan D., Malan D., Catapano F., Ghé C., Deghenghi R., Ghigo E., Muccioli G. Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln(14)-ghrelin. Eur J Pharmacol 2003, 476:87-95.
17. Cassoni P., Papotti M., Ghe C., Catapano F., Sapino A., Graziani A., Deghenghi R., Reissmann T., Ghigo E., Muccioli G. Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines. J Clin Endocrinol Metab 2001, 86:1738-1745.
18. Jeffery P.L., Herington A.C., Chopin L.K. The potential autocrine/paracrine roles of ghrelin and its receptor in hormone-dependent cancer. Cytokine Growth Factor Rev 2003, 14:113-122.
19. McKee K.K., Palyha O.C., Feighner S.D., Hreniuk D.L., Tan C.P., Phillips M.S., Smith R.G., Van der Ploeg L.H., Howard A.D. Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors. Mol Endocrinol 1997, 11(4):415-423.
20. Howard A.D., Feighner S.D., Cully D.F., Arena J.P., Liberator P.A., Rosenblum C.I., Hamelin M., Hreniuk D.L., Palyha O.C., Anderson J., Paress P.S., Diaz C., Chou M., Liu K.K., McKee K.K., Pong S.S., Chaung L.Y., Elbrecht A., Dashkevicz M., Heavens R., et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996, 273:974-977.
21. Smith R.G., Jiang H., Sun Y. Developments in ghrelin biology and potential clinical relevance. Trends Endocrinol Metab 2005, 16(9):436-442.
22. Cruz C.R.Y., Smith R.G. The growth hormone secretagogue receptor. Vitam Horm 2007, 77:47-88.
23. Date Y., Kojima M., Hosoda H., Sawaguchi A., Mondal S.M., Suganuma T., Matsukura S., Kangawa K., Nakazato M. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 2000, 141:4255-4261.
24. Ariyasu H., Takaya K., Tagami T., Ogawa Y., Hosoda K., Akamizu T., Suda M., Koh T., Natsui K., Toyooka S., Shirakami G., Usui T., Shimatsu A., Doi K., Hosoda H., Kojima M., Kangawa K., Nakao K. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin like immunoreactivity levels in humans. J Clin Endocrinol Metab 2001, 86:4753-4758.
25. Krsek M., Rosicka M., Haluzik M., Svobodová J., Kotrlíková E., Justová V., Lacinová Z., Jarkovská Z. Plasma ghrelin levels in patients with short bowel syndrome. Endocr Res 2002, 28:27-33.
26. Leonetti F., Silecchia G., Iacobellis G., Ribaudo M.C., Zappaterreno A., Tiberti C., Iannucci C.V., Perrotta N., Bacci V., Basso M.S., Basso N., Di Mario U. Different plasma ghrelin levels after laparoscopic gastric bypass and adjustable gastric banding in morbid obese subjects. J Clin Endocrinol Metab 2003, 88:4227-4231.
27. Cowley M.A., Smith R.G., Diano S., Tschöp M., Pronchuk N., Grove K.L., Strasburger C.J., Bidlingmaier M., Esterman M., Heiman M.L., Garcia-Segura L.M., Nillni E.A., Mendez P., Low M.J., Sotonyi P., Friedman J.M., Liu H., Pinto S., Colmers W.F., Cone R.D., et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 2003, 37:649-661.
28. Korbonits M., Bustin S.A., Kojima M., Jordan S., Adams E.F., Lowe D.G., Kangawa K., Grossman A.B. The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J Clin Endocrinol Metab 2001, 86:881-887.
29. Volante M., Fulcheri E., Allia E., Cerrato M., Pucci A., Papotti M. Ghrelin expression in fetal, infant, and adult human lung. J Histochem Cytochem 2002, 50:1013-1021.
30. Gnanapavan S., Kola B., Bustin S.A., Morris D.G., McGee P., Fairclough P., Bhattacharya S., Carpenter R., Grossman A.B., Korbonits M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002, 87(6):2988.
31. Lucchesi P.A. Growth hormone-releasing peptides and the heart: secretagogues or cardioprotectors?. Cardiovasc Res 2004, 61(1):30-38.
32. Volante M., Allia E., Gugliotta P., Funaro A., Broglio F., Deghenghi R., Muccioli G., Ghigo E., Papotti M. Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab 2002, 87:1300-1308.
33. Wierup N., Svensson H., Mulder H., Sundler F. The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept 2002, 107:63-69.
34. Volante M., Allia E., Fulcheri E., Cassoni P., Ghigo E., Muccioli G., Papotti M. Ghrelin in fetal thyroid and follicular tumors and cell lines: expression and effects on tumor growth. Am J Pathol 2003, 162(2):645-654.
35. Papotti M., Ghè C., Cassoni P., Catapano F., Deghenghi R., Ghigo E., Muccioli G. Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab 2000, 85(10):3803-3807.
36. Kanamoto N., Akamizu T., Hosoda H., Hataya Y., Ariyasu H., Takaya K., Hosoda K., Saijo M., Moriyama K., Shimatsu A., Kojima M., Kangawa K., Nakao K. Substantial production of ghrelin by a human medullary thyroid carcinoma cell line. J Clin Endocrinol Metab 2001, 86(10):4984-4990.
37. Rindi G., Torsello A., Locatelli V., Solcia E. Ghrelin expression and actions: a novel peptide for an old cell type of the diffuse endocrine system. Exp Biol Med 2004, 229(10):1007-1016.
38. Raghay K., García-Caballero T., Nogueiras R., Morel G., Beiras A., Diéguez C., Gallego R. Ghrelin localization in rat and human thyroid and parathyroid glands and tumors. Histochem Cell Biol 2006, 125(3):239-246.
39. Caminos J.E., Tena-Sempere M., Gaytan F., Sanchez-Criado, Barreiro M.L., Nogueiras R., Casanueva F., Aguilar E., Diéguez C. Expression of ghrelin in the cyclic and pregnant rat ovary. Endocrinology 2003, 144:1594-1602.
40. Gaytan F., Barreiro M.L., Chopin L.K., Herington A.C., Morales C., Pinilla L., Casanueva F.F., Aguilar E., Diéguez C., Tena-Sempere M. Immunolocalization of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor in the cyclic human ovary. J Clin Endocrinol Metab 2003, 88:879-887.
41. Barreiro M.L., Gaytan F., Caminos J.E., Pinilla L., Casanueva F.F., Aguilar E., Diéguez C., Tena-Sempere M. Cellular location and hormonal regulation of ghrelin expression in rat testis. Biol Reprod 2002, 67:1768-1776.
42. Tena-Sempere M., Barreiro M.L., Gonzalez L.C., Gaytán F., Zhang F.P., Caminos J.E., Pinilla L., Casanueva F.F., Diéguez C., Aguilar E. Novel expression and functional role of ghrelin in rat testis. Endocrinology 2002, 143:717-725.
43. Mori K., Yoshimoto A., Takaya K., Hosoda K., Ariyasu H., Yahata K., Mukoyama M., Sugawara A., Hosoda H., Kojima M., Kangawa K., Nakao K. Kidney produces a novel acylated peptide, ghrelin. FEBS Lett 2000, 486(3):213-216.
44. Gualillo O., Caminos J.E., Blanco M., Garcìa-Caballero T., Kojima M., Kangawa K., Dieguez C., Casanueva F. Ghrelin, a novel placental-derived hormone. Endocrinology 2001, 142:788-794.
45. Dixit V.M., Schaffer E.M., Taub D.D. Ghrelin is expressed and secreted from human T lymphocytes and inhibits activation and leptin induced inflammatory cytokine expression via functional, lipid raft-associated growth hormone secretagogue receptors (GHS-R). Proceedings of the 85th Annual Meeting of the Endocrine Society 2003, OR51-3.
46. Hattori N., Saito T., Yagyu T., Jiang B.H., Kitagawa K., Inagaki C. GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab 2001, 86:4284-4291.
47. Nikolopoulos D., Theocharis S., Kouraklis G. Ghrelin's role on gastrointestinal tract cancer. Surg Oncol 2010, 19(1):e2-10.
48. Hosoda H., Kojima M., Kangawa K. Biological, physiological, and pharmacological aspects of ghrelin. J Pharmacol Sci 2006, 100(5):398-410.
49. van der Lely A.J., Tschöp M., Heiman M.L., Ghigo E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 2004, 25(3):426-457.
50. Korbonits M., Goldstone A.P., Gueorguiev M., Grossman A.B. Ghrelin-a hormone with multiple functions. Front Neuroendocrinol 2004, 25:27-68.
51. Korbonits M., Kojima M., Kangawa K., Grossman A.B. Presence of ghrelin in normal and adenomatous human pituitary. Endocr 2001, 14(1):101-104.
52. Kim K., Arai K., Sannot N., Osamura R.Y., Teramoto A., Shibasaki T. Ghrelin and GHSR mRNA expression in human pituitary adenomas. Clin Endocrinol 2001, 54:759-768.
53. Wu J.T., Kral J.G. Ghrelin: integrative neuroendocrine peptide in health and disease. Ann Surg 2004, 239(4):464-474.
54. C.A.Leontiou, Franchi G., Korbonits M. Ghrelin in neuroendocrine organs and tumors. Pituitary 2007, 10(3):213-225.
55. Wasko R., Jaskula M., Kotwicka M., Andrusiewicz M., Jankowska A., Liebert W., Sowinski J. The expression of ghrelin in somatotroph and other types of pituitary adenomas. Neuro Endocrinol Lett 2008, 29(6):929-938.
56. Garcia A., Alvarez C.V., Smith R.G., Dieguez C. Regulation of Pit-1 expression by ghrelin and GHRP-6 through the GH secretagogue receptor. Mol Endocrinol 2001, 15:1484-1495.
57. Korbonits M., Jacobs R.A., Aylwin S.J., Burrin J.M., Dahia P.L., Monson J.P., Honegger J., Fahlbush R., Trainer P.J., Chew S.L., Besser G.M., Grossman A.B. Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. J Clin Endocrinol Metab 1998, 83:3624-3630.
58. Skinner M.M., Nass R., Lopes B., Laws E.R., Thorner M.O. Growth hormone secretagogue receptor expression in human pituitary tumors. J Clin Endocrinol Metab 1998, 83(12):4314-4320.
59. Adams E.F., Huang B., Buchfelder M., Howard A., Smith R.G., Feighner S.D., van der Ploeg L.H., Bowers C.Y., Fahlbusch R. Presence of growth hormone secretagogue receptor messenger ribonucleic acid in human pituitary tumors and rat GH3 cells. J Clin Endocrinol Metab 1998, 83(2):638-642.
60. Cassoni P., Papotti M., Catapano F., Ghè C., Deghenghi R., Ghigo E., Muccioli G. Specific binding sites for synthetic growth hormone secretagogues in non-tumoral and neoplastic human thyroid tissue. J Endocrinol 2000, 165:139-146.
61. Jeffery P.L., Herington A.C., Chopin L.K. Expression and action of the growth hormone releasing peptide ghrelin and its receptor in prostate cancer cell lines. J Endocrinol 2002, 172:R7-R11.
62. Cassoni P., Ghe C., Marrocco T., Tarabra E., Allia E., Catapano F., Deghenghi R., Ghigo E., Papotti M., Muccioli G. Expression of ghrelin and biological activity of specific receptors for ghrelin and des-acyl ghrelin in human prostate neoplasms and related cell lines. Eur J Endocrinol 2004, 150:173-184.
63. Yeh A.H., Jeffery L.P., Duncan R.P., Herington A.C., Chopin L.K. Ghrelin and a novel preproghrelin isoform are highly expressed in prostate cancer and ghrelin activates mitogen-activated protein kinase in prostate cancer. Clin Cancer Res 2005, 11(23):8295-8303.
64. Papotti M., Cassoni P., Volante M., Deghenghi R., Muccioli G., Ghigo E. Ghrelin-producing endocrine tumors of the stomach and intestine. J Clin Endocrinol Metab 2001, 86:5052-5059.
65. Murata M., Okimura Y., Iida K., Matsumoto M., Sowa H., Kaji H., Kojima M., Kangawa K., Chihara K. Ghrelin modulates the downstream of insulin signaling in hepatoma cells. J Biol Chem 2002, 277:5667-5674.
66. Iwakura H., Hosoda K., Doi R., Komoto I., Nishimura H., Son C., Fujikura J., Tomita T., Takaya K., Ogawa Y., Hayashi T., Inoue G., Akamizu T., Hosoda H., Kojima M., Kangawa K., Imamura M., Nakao K. Ghrelin expression in islet cell tumors: augmented expression of ghrelin in a case of glucagonoma with multiple endocrine neoplasm type I. J Clin Endocrinol Metab 2002, 87:4885-4888.
67. Ekeblad S., Lejonklou M.H., Grimfjard P., Johansson T., Eriksoon B., Grimelius L., Stridsberg M., Stlberg P., Skogseid B. Co-expression of ghrelin and its receptor in pancreatic endocrine tumors. Clin Endocrinol 2007, 66:115-122.
68. Aydin S., Ozercan I.H., Dagli F., Aydin S., Dogru O., Celebi S., Akin O., Guzel S.P. Ghrelin immunohistochemistry of gastric adenocarcinoma and mucoepidermoid carcinoma of salivary gland. Biotech Histochem 2005, 80(3-4):163-168.
69. Huang Qi., Fan Yue-Zu, Ge Bu-Jun, Zhu Qin, Tu Zhi-Yuan Circulating ghrelin in patients with gastric or colorectal cancer. Dig Dis Sci 2007, 52:803-809.
70. D'Onghia V., Leoncini R., Carli R., Santoro A., Giglioni S., Sorbellini F., Marzocca G., Bernini A., Campagna S., Marinello E., Vannoni D. Circulating gastrin and ghrelin levels in patients with colorectal cancer: correlation with tumour stage, Helicobacter pylori infection and BMI. Biomed Pharmacother 2007, 61:137-141.
71. Ji Y.A., Min-Gew Ch., Jae H.N., Sohn T.S., Jin D.K., Kim S. Clinical significance of ghrelin concentration of plasma and tumor tissue in patients with gastric cancer. J Surg Res 2007, 143:344-349.
72. Mottershead M., Karteris E., Barclay J.Y., Suortamo S., Newbold M., Randeva H., Nwokolo C.U. Immunohistochemical and quantitative mRNA assessment of ghrelin expression in gastric and oesophageal adenocarcinomas. J Clin Pathol 2007, 60:405-409.
73. Wang Z., Wang W., Qiu W., Fan Y., Zhao J., Wang Y., Zheng Q. Involvement of ghrelin-growth hormone secretagogue receptor system in pathoclinical profiles of digestive system cancer. Acta Biochim Biophys Sin 2007, 39:992-998.
74. Jeffery P.L., Murray R.E., Yeh A.H., McNamara J.F., Duncan R.P., Francis G.D., Herington A.C., Chopin L.K. Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines. Endocr Relat Cancer 2005, 12(4):839-850.
75. Gaytan F., Barreiro M.L., Caminos J.E., Chopin L.K., Herington A.C., Morales C., Pinilla L., Paniagua R., Nistal M., Casanueva F.F., Aguilar E., Diéguez C., Tena-Sempere M. Expression of ghrelin and its functional receptor, the type 1a growth hormone secretagogue receptor, in normal human testis and testicular tumors. J Clin Endocrinol Metab 2004, 89:400-409.
76. Gaytan F., Morales C., Barreiro M.L., Chopin L.K., Herington A.C., Casanueva F.F., Aguilar E., Dieguez C., Tena-Sempere M. Expression of growth hormone secretagogue receptor type 1a, the functional ghrelin receptor, in human ovarian surface epithelium, mullerian duct derivatives, and ovarian tumors. J Clin Endocrinol Metab 2005, 90:1798-1804.
77. Barreiro M.L., Gaytan F., Castellano J.M., Suominen J.S., Roa J., Gaytan M., Aguilar E., Dieguez C., Toppari J., Tena-Sempere M. Ghrelin inhibits the proliferative activity of immature Leydig cells in vivo and regulates stem cell factor messenger ribonucleic acid expression in rat testis. Endocrinology 2004, 145:4825-4834.
78. Ghe C., Cassoni P., Catapano F., Marrocco T., Deghenghi R., Ghigo E., Muccioli G., Papotti M. The antiproliferative effect of synthetic peptidyl GH secretagogues in human CALU-1 lung carcinoma cells. Endocrinology 2002, 143:484-491.
79. Cassoni P., Allia E., Marrocco T., Ghè C., Ghigo E., Muccioli G., Papotti M. Ghrelin and cortistatin in lung cancer: expression of peptides and related receptors in human primary tumors and in vitro effect on the H345 small cell carcinoma cell line. J Endocrinol Invest 2006, 29(9):781-790.
80. Karapanagiotou E.M., Polyzos A., Dilana K.D., Gratsias I., Boura P., Gkiozos I., Syrigos K.N. Increased serum levels of ghrelin at diagnosis mediate body weight loss in non-small cell lung cancer (NSCLC) patients. Lung Cancer 2009, 66(3):393-398.
81. Arnaldi G., Mancini T., Kola B., Appolloni G., Freddi S., Concettoni C., Bearzi I., Masini A., Boscaro M., Mantero F. Cyclical Cushing's syndrome in a patient with a bronchial neuroendocrine tumor (typical carcinoid) expressing ghrelin and growth hormone secretagogue receptors. J Clin Endocrinol Metab 2003, 88(12):5834-5840.
82. Takahashi K., Furukawa C., Takano A., Ishikawa N., Kato T., Hayama S., Suzuki C., Yasui W., Inai K., Sone S., Ito T., Nishimura H., Tsuchiya E., Nakamura Y., Daigo Y. The neuromedin U-growth hormone secretagogue receptor 1b/neurotensin receptor 1 oncogenic signaling pathway as a therapeutic target for lung cancer. Cancer Res 2006, 66(19):9408-9419.
83. Dagli A.F., Aydin S., Karaoglu A., Akpolat N., Ozercan I.H., Ozercan M.R. Ghrelin expression in normal kidney tissue and renal carcinomas. Pathol Res Pract 2009, 205:165-173.
84. Dixit V.D., Weeraratna A.T., Yang H., Bertak D., Cooper-Jenkins A., Riggins G.J., Eberhart C.G., Taub D.D. Ghrelin and the growth hormone secretagogue receptor constitute a novel autocrine pathway in astrocytoma motility. J Biol Chemistry 2006, 281(24):16681-16690.
85. de Herder W.W. Biochemistry of neuroendocrine tumors. Best Pract Res Clin Endocrinol Metab 2007, 21(1):33-41.
86. Waseem T., Javaid-ur-Rehman, Ahmad F., Azam M., Qureshi A.M. Role of ghrelin axis in colorectal cancer: a novel association. Peptides 2008, 29:1369-1376.
87. Nanzer A.M., Khalaf S., Mozid A.M., Fowkes R.C., Patel M.V., Burrin J.M., Grossman A.B., Korbonits M. Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway. Eur J Endocrinol 2004, 151:233-240.
88. Raghay K., García-Caballero T., Nogueiras R., Morel G., Beiras A., Diéguez C., Gallego R. Ghrelin localization in rat and human thyroid and parathyroid glands and tumours. Histochem Cell Biol 2006, 125(3):239-246.
89. Duxbury M.S., Waseem T., Ito H., Robinson M.K., Zinner M.J., Ashley S.W., Whang E.E. Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness. Biochem Biophys Res Commun 2003 Sep 19, 309(2):464-468.
90. Delhanty P.J.D., van Koetsveld P.M., Gauna C., van de Zande B., Vitale G., Hofland L.J., van der Lely A.J. Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway. Am J Physiol Endocrinol Metab 2007, 293:E302-E309.
91. De Vriese C., Delporte C. Autocrine proliferative effect of ghrelin on leukemic HL-60 and THP-1 cells. J Endocrinol 2007, 192:199-205.
92. Barzon L., Pacenti M., Masi G., Stefani A.L., Fincati K., Palù G. Loss of growth hormone secretagogue receptor 1a and overexpression of type 1b receptor transcripts in human adrenocortical tumors. Oncology 2005, 68(4-6):414-421.