Growth hormone-releasing hormone and extra-pituitary tumorigenesis: Therapeutic and diagnostic applications of growth hormone-releasing hormone antagonists

Expert Opinion on Investigational Drugs

Volumn 12, Issue 8, 2003, Pages 1385-1394

  Kiaris, Hippokratis ^a   Koutsilieris, Michael ^a   Kalofoutis, Anastasios ^a   Schally, Andrew V ^b  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Anticancer therapy; Autocrine; GHRH; GHRH receptor; Neuropeptides

Indexed keywords

ANTINEOPLASTIC AGENT; CYCLIC AMP; FOLLITROPIN; GROWTH HORMONE; GROWTH HORMONE RELEASING FACTOR; GROWTH HORMONE RELEASING FACTOR RECEPTOR; HORMONE ANTAGONIST; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; JV 1 38; MZ 5 156; NEUROPEPTIDE; PEPTIDE HISTIDINE ISOLEUCINE; PEPTIDE HISTIDINE METHIONINE; SOMATOMEDIN B; SOMATOMEDIN C; UNCLASSIFIED DRUG; VASCULOTROPIN; VASOACTIVE INTESTINAL POLYPEPTIDE;

ANTINEOPLASTIC ACTIVITY; AUTOCRINE EFFECT; BRAIN CANCER; BREAST CANCER; CANCER DIAGNOSIS; CANCER THERAPY; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; EWING SARCOMA; EXPERIMENTAL NEOPLASM; GROWTH HORMONE RELEASE; HORMONAL CARCINOGENESIS; HORMONAL REGULATION; HORMONE ACTION; HORMONE RELEASE; HORMONE SYNTHESIS; HUMAN; HYPOPHYSIS; KIDNEY CANCER; LUNG SMALL CELL CANCER; NEUROENDOCRINOLOGY; NONHUMAN; OSTEOSARCOMA; OVARY CANCER; PANCREAS CANCER; PARACRINE SIGNALING; PROSTATE CANCER; REVIEW; TUMOR CELL;

ANIMALS; AUTOCRINE COMMUNICATION; CELL DIVISION; GROWTH HORMONE; GROWTH HORMONE-RELEASING HORMONE; HORMONE ANTAGONISTS; HUMANS; INSULIN-LIKE GROWTH FACTOR I; NEOPLASMS; PITUITARY GLAND; TUMOR CELLS, CULTURED;

EID: 0041633498     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.12.8.1385     Document Type: Review

References (85)

1. SCHALLY AV, COMARUSCHALLY AM: Agonistic analogues of growth hormone - releasing hormone (GH-RH): endocrine and growth studies. In: Growth Hormone Secretagogues in Cinical Practice. BB Bercu, RF Walker (Eds), Marcel Dekker, New York (1998):14-31.
2. SCHALLY AV, STEELMAN S, BOWERS CY. Effect of hypothalamic extracts on the release of growth hormone in vitro. Proc. Soc. Exp. Biol. Med. (1965) 119:208-212.
3. KRULICH L, DHARIWAL APS, MCCANN SM: Stimulatory and inhibitory effects of purified hypothalamic extracts on growth hormone release from rat pituitary in vitro. Endocrinology (1968) 83:783-790.
4. SCHALLY AV, VARGA JL: Antagonistic analogues of growth hormone - releasing hormone: New potential antitumor agents. Trends Endoctrinol. Metab. (1999) 10:383-391.
5. KOUTSILIERIS M, MASTROGAVRAKIS G, LEMBESSIS P, SOURLA A, MILIGOS S, MICHALAS S: Increased insulin-like growth Factor I activity can rescue KLE endometrial-like cells from apoptosis. Mol. Med. (2001) 7:20-26.
6. MITSIADES C, KOUTSILIERIS M: Molecular biology and cellular physiology of refractoriness to androgen ablation therapy in advanced prostate cancer. Expert Opin. Invest. Drugs (2001) 6:1099-1115.
7. KOUTSILIERIS M, MITSIADES C, SOURLA A. Insulin-like growth Factor I and urokinase-type plasminogen activator bioregulation system as a survival mechanism of prostate cancer cells in osteoblastic metastases: development of anti-survival factor therapy for hormone-refractory prostate cancer. Mol. Med. (2000) 6:251-167.
8. KOUTSILIERIS M, REYES-MORENO C, CHOKI I, SOURLA A, DOILLON C, PAVLIDES N: Chemotherapy cytotoxicity of human MCF-7 and MDA-MB 231 breast cancer cells is altered by ostooblasts-derived growth factors. Mol. Med. (1999) 5:86-97.
9. REYES-MORENO C, SOURLA A. CHOKI I, DOILLON C, KOUTSILIERIS M: Osteoblast-derived survival factors protect PC-3 prostate cancer cells from adriamycin apoptosis. Urology (1998) 52:341-347.
10. FROHMAN LA, SZABO M: Ectopic production of growth hormone releasing fiictor by carcinoid and pancreatic islet tumors associated with acromegaly. Prog. Clin. Biol. Res. (1981) 74:259-271.
11. RIVIER J, SPIESS J, THORNER. M, VALE W: Characterisation of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature (1982) 300:276-278.
12. GUILLEMIN R. BRAZEAU P, BOHLEN P, ESCH F, LING N, WEHRENBERG WB: Growth hormone releasing factor from a human pancreatic tumor that caused acromegaly Science (1982) 218:585-587.
13. LING N, ESCH F, BOHLEN R. BRAZEAU P, WEHRENBERG WB, GUILLEMIN R: Isolation, primary structure, and synthesis of human hypothalamic somatocrinin: growth hormone-releasing factor. Proc. Natl. Acad. Sci. USA (1984) 81:4302-4306.
14. GUILLEMIN R. ZEYTIN F, LING N et al.: Growth hormone-releasing factor. Chemistry and Physiology. Proc. Soc. Exp. Biol. Med. (1984) 175:407-413.
15. LOSA M, VON WERDER K: Pathophysiology and clinical aspects of the ectopic GH-releasing hormone syndrome. Clin. Endocrinol. (Oxf.) (1997) 47:123-135.
16. HAMMER RE, BRINSTER RL, ROSENFELD MG, EVANS RM, MAYO KE: Expression of human growth hormone - releasing factor in transgenic mice results in increased somatic growth. Nature (1985) 315:413-416.
17. FROHMAN LA, KINEMAN RD: Growth hormone-releasing hormone and pituitary somatotrope proliferation. Minerva Endocrinol. (2002) 27:277-285.
18. FROHMAN LA, KINEMAN RD: Growth hormone-releasing hormone and pituitary development, hyperplasia and tumorigenesis. Trends Endocrinol. Metab. (2002) 13:299-303.
19. MAYO KE, MILLER T, DEALMEIDA V, GODFREY P, ZHENG J, CUNHA SR: Regulation of the pituitary somatotroph cell by GHRH and its receptor. Recent Prog. Horm. Res. (2000) 55:237-266; discussion 266-267.
20. DOWNS TR, FROHMAN LA. Evidence for a defect in growth hormone-releasing factor signal transduction in the dwarf (dw/dw) rat pituitary. Endocrinology (1991) 129:58-67.
21. TIERNEY T, ROBINSON IC: Increased lactotrophs despite decreased somatotrophs in the dwarf (dw/dw) rat: a defect in the regulation of lactotroph/somatotroph cell fate? J. Endocrinol. (2002) 175:435-446.
22. MUTSUGA N, IWASAKI Y, MORISHITA M et al.: Homeobox protein Gsh-1-dependent regulation of the rat GHRH gene promoter. Mol. Endocrinol. (2001) 15:2149-2156.
23. FURSTENBERGER G, SENN HJ: Insulin-like growth factors and cancer. Lancet Oncol. (2002) 3:298-302.
24. HADSELL DL, ABDEL-FATTAH G: Regulation of cell apoptosis by insulin-like growth Factor I. Adv. Exp. Med. Biol. (2001) 501:79-85.
25. POLLAK MN, SEMAW, RICHARD M, TETENES E, BELL R: Inhibition of metastaic behaviour of murine osteosarcoma by hypophysectomy. J. Natl. Cancer Inst. (1992) 84:966-971.
26. DEITEL K, DANTZER D, FERGUSON P et al.: Reduced growth of human sarcoma xenografts in hosts homozygous for the lit mutation J. Surg. Oncol. (2002) 81:75-79.
27. BUGNI JM, POOLE TM, DRINKWATER NR: The little mutation suppresses DEN-induced hepatocarcinogenesis in mice and abrogates genetic and hormonal modulation of susceptibility. Carcinogenesis (2001) 22:1853-1862.
28. YANG XF, BEAMER WG, HUYNH H, POLLAK M: Reduced growth of human breast cancer xenografts in hosts homozygous for the lit mutation. Cancer Res. (1996) 56:1509-1511.
29. PINSKI J, SCHALLY AV, GROOT K et al.: Inhibition of growth of human osteosarcomas by antagonists of growth hormone-releasing hormone. J. Natl. Canc. Inst. (1995) 87:1787-1794.
30. JUNGWIRTH A, SCHALLY AV, PINSKI AV et al.: Inhibition of in vivo proliferation of androgen-independent prostate cancers by an antagonist of growth hormone-releasing hormone Br. J. Cancer (1997) 75:1585-1592.
31. LAMHARZI N, SCHALLY AV, KOPPAN M, GROOT K: Growth hormone-releasing hormone antagonist MZ-5-156 inhibits growth of DU-145 human androgen-independent prostate carcinoma in nude mice and suppresses the levels and mRNA expression of insulin-like growth factor II in tumors. Proc. Natl. Acad. Sci. USA (1998) 95:8864-8868.
32. SZEPESHAZI K, SCHALLY AV, ARMATIS P et al.: Antagonists of GHRH decrease production of GH and IGF-I in MXT mouse mammary cancers and inhibit tumor growth. Endocrinology (2001) 142:4371-4378.
33. JUNGWIRTH A. SCHALLY AV, PINSKI J, GROOT K, ARMATIS P, HALMOS G: Growth hormone-releasing hormone antagonist MZ-4-71 inhibits in vivo proliferation of Caci-I renal adenocarcinoma. Proc. Natl. Acad. Sci. USA (1997) 94:5810-5813.
34. PINSKI J, SCHALLY AV, JUNGWIRTH A et al.: Inhibition of growth of small cell and non-small cell lung carcinomas by antagonists of growth hormone-releasing hormone (GH-RH). Int. J. Oncol. (1996) 9-1099-1105.
35. KAHAN Z, VARGA JL, SCHALLY AV et al: Antagonists of growth hormone-releasing hormone arrest the growth of MDA-MB-468 estrogen - independent human breast cancers in nude mice. Breast Canc. Res. Treat. (2000) 60:71-79.
36. MARGIORIS NM, BROCKMANN G, BOHLER HCL Jr, GRINO M, VAMVAKOPOULOS N, CHROUSOS GP: Expression and localisation of growth hormone-releasing hormone messanger ribonucleic acid in rat placenta: in vitro secretion and regulation of its peptide product. Endocrinology (1990) 126:151-158.
37. BERRY SA, PESCOVITZ OH: Identification of a rat GHRH-like substance and its mRNA in rat testis. Endocrinology (1988) 126:661-663.
38. MORETTI C, FABBRI A. GNESSI L et al.: Immunohistochemical localisation of growth hormone-releasing hormone in human gonads. J. Endocrinol Invest. (1990) 13:301-305.
39. STEPHANOU A, KNIGHT RA, LIGHTMAN SL: Production of growth hormone - releasing hormone -like peptide and its mRNA by human lymphocytes. Neuroendocrinology (1991) 53:628-633.
40. CIAMPANI T, FABBRI A, ISIDORI A. DUFAU ML: Growth hormone-releasing hormone is produced by rat Leydig cell in culture and acts as a positive regulator of Leydig cell function. Endocrinology (1992) 131:2785-2792.
41. BAGNATO A, MORETTI C, OHNISHI J, FRAJESE G, CATT KJ: Expression of the growth hormone releasing hormone and its peptide product in the rat ovary. Endocrinology (1992) 130:1097-1102.
42. BAGNATO A, MORETTI C, FRAJESE G, CATT KJ: Gonadotropin-induced expression of receptors for growth hormone-releasing factor in cultured granulosa cells. Endocrinology (1991) 128:2889-2894.
43. GAYLINN BD: Molecular and cell biology of the growth hormone-releasing hormone receptor. Growth Horm. IGF Res. (1999) 9:37-44.
44. MORETTI C, RAGNATO A, SOLAN N, FRAJESE G, CATT KJ: Receptor-mediated actions of growth hormone releasing factor on granulosa cell differentiation. Endocrinology (1990) 127:2117-2126.
45. KHORRAM O, GARTHWAITE M, GROSEN E, GOLOS T: Human uterine and ovarian expression of growth hormone-releasing hormone messenger RNA in benign and malignant gynecological conditions. Fertil. Steril. (2001) 75:174-179.
46. KHORRAM O, GARTHWAITE M, GOLOS T: The influence of aging and sex hormones on expression of growth hormone-releasing hormone in the human immune system. J. Clin. Endocrinol. Metab. (2001) 86:3157-3161.
47. KIARIS H, SCHALLY AV, ARMATIS P: Direct action of growth hormone-releasing hormone agonist JI-38 on normal human fibroblasts: Evidence from studies on cell proliferation and c-myc oncogene expression. Regulatory Peptides (2001) 96:119-124.
48. KAHAN Z, ARENCIBIA JM, CZERNUS VJ et al.: Expression of growth hormone - releasing hormone (GH-RH) messenger ribonucleic acid and the presence of biologically active GH-RH in human breast, endometrial, and ovarian cancers. J. Clin. Endocrinology Metabol. (1999) 84:582-589.
49. KIARIS H, SCHALLY AV, VARGA JL. GROOT K, ARMATIS P: Growth hormone - releasing hormone: An autocrine growth factor for small cell lung carcinoma. Proc. Natl. Acad. Sci. USA (1999) 96:3098-3103.
50. CHOPIN LK, HERINGTON AC: A potential autocrine pathway for growth hormone releasing hormone (GHRH) and its receptor in human prostate cancer cell lines. Prostate (2001) 49:116-121.
51. CHATZISTAMOU I, SCHALLY AV, PAFITI A, KIARIS H, KOUTSELINI H: Expression of growth hormone-releasing hormone in human primary endometrial carcinomas. Eur. J. Endocrinol. (2002) 147:381-386.
52. HALMOS G, SCHALLY AV, CZOMPOLY T, KRUPA M, VARGA JL, REKASI Z: Expression of growth hormone-releasing hormone and its receptor splice variants in human prostate cancer J. Clin. Endocrinol. Metab. (2002) 87:4707-4714.
53. PLONOWSKI A, SCHALLY AV, BUSTO R, KRUPA M, VARGA JL, HALMOS G: Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers. Peptides (2002) 23:1127-1133.
54. BUSTO R, SCHALLY A. BRACZKOWSKI R et al.: Expression of mRNA for growth hormone-releasing hormone and splice variants of GHRH receptors in human malignant bone rumors. Regul. Pept. (2002) 108:47-53.
55. BUSTO R, SCHALLY AV, VARGA JL et al.: The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas. Proc. Natl. Acad. Sci. USA (2002) 99:11866-11871.
56. HALMOS G, SCHALLY AV, CZOMPOLY T, KRUPA M, VARGA JL, REKASI Z: Expression of growth hormone-releasing hormone and its receptor splice variants in human prostate cancer. J. Clin. Endocrinol. Metab. (2002) 87:4704-4714.
57. PLONOWSKI A, SCHALLY AV, LETSCH M et al.: Inhibition of proliferation of PC-3 human prostate cancer by antagonists of growth hormone-releasing hormone: lack of correlation with the levels of serum IGF-I and expression of tumoral. IGF-II and vascular endothelial growth factor. Prostate (2002) 52:173-182.
58. PLONOWSKI A. VARGA JL, SCHALLY AV, KRUPA M, GROOT K, HALMOS G: Inhibition of PC-3 human prostate cancers by analogs of growth hormone-releasing hormone (GH-RH) endowed with vasoactive intestinal peptide (VIP) antagonistic activity. Int. J. Cancer (2002) 98(4):624-629.
59. CHATZISTAMOU I, SCHALLY AV, VARGA JL et al.: Inhibition of growth and metastases of MDA-MB-435 human estrogen-independent breast cancers by an antagonist of growth hormone-releasing hormone. Anti-Cancer Drugs (2001) 12:761-768.
60. ZEITLER P, SIRIWARDANA G.. Antagonism of endogenous growth hormone-releasing hormone (GHRH) leads to reduced proliferation and apoptosis in MDA231 breast cancer cells. Endocrine (2002) 18:85-90.
61. CHATZISTAMOU I, SCHALLY AV, VARGA JL et al.: Antagonists of growth hormone-releasing hormone and somatostatin analog RC-160 inhibit the growth of the OV-1063 human epithelial ovarian cancer cell line xenografted into nude mice. J. Clin. Endocrinol Metab. (2001) 86:2144-2152.
62. CSERNUS VJ, SCHALLY AV, KIARIS H, ARMATIS P: Inhibition of growth, production of insulin-like growth factor-II (IGF-II), and expression of IGF-II mRNA of human cancer cell fines by antagonistic analogues of growth hormone-releasing hormone in vitro Proc. Natl. Acad. Sci. USA (1999) 96:3098-3103.
63. SZEPESHAZI K, SCHALLY AV, GROOT K, ARMATIS P, HEBERT F, HALMOS G: Antagonists of growth hormone - releasing hormone (GH-RH) inhibit in vivo proliferation of experimental pancreatic cancers and decrease IGF-II levels in tumors. Eur. J. Cancer (2000) 36:128-136.
64. SZEPESHAZI K, SCHALLY AV, GROOT K et al.: Antagonism of growth hormone-releasing hormone (GH-RH) inhibit IGF-II production and growth of HT-29 human colon cancers. Br. J. Cancer (2000) 82:1724-1731.
65. BRACZKOWSKI R, SCHALLY AV, PLONOWSKI A et al.: Inhibition of proliferation in human MNNG/HOS osteosarcoma and SK-ES-1 Ewing sarcoma cell lines in vitro and in vivo by antagonists of growth hormone-releasing hormone. Cancer (2002) 95:1735-1745.
66. KIARIS H, SCHALLY AV: Decrease in telomerase activity in U-87MG human glioblastomas after treatment with an antagonist of growth hormone-releasing hormone. Proc. Natl. Acad. Sci .USA (1999) 96:226-231.
67. KIARIS H, SCHALLY AV, VARGA JL: Antagonists of growth hormone-releasing hormone inhibit the growth of U-87MG human glioblastoma in nude mice. Neoplasia (2000) 2:242-250.
68. CHATZISTAMOU I, SCHALLY AV, VARGA JL: Inhibition of growth and reduction in tumorigenicity of UCI-107 ovarian cancer by antagonists of growth hormone-releasing hormone and vasoactive intestinal peptide. J. Cancer Res. Clin. Oncol. (2001) 127:645-652.
69. LETSCH M, SCHALLY AV, BUSTO R, BAJOAM, VARGA JL: Growth hormone releasing hormone antagonists inhibit the proliferation of androgen - dependent and-independent prostate cancers. Proc. Natl. Acad. Sci. USA (2002).
70. MAYO KE: Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol. Endocrinol. (1992) 6:1734-1744.
71. GAYLINN BD, HARRISON JK, ZYSK JR, LYONS CE, LYNCH KR, THORNER MO: Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone. Mol. Endocrinol. (1993) 7:77-84.
72. MAYO KE, MILLER TL, DE ALMEIDA V, ZHENG J, GODFREY PA. The growth hormone releasing hormone receptor signal transduction, gene expression, and physiological function in growth regulation. Ann. NY Acad. Sci. (1996) 805:184-203.
73. MATSUBARA S, MAKOTO S, MIZOBUCHI M, NIIMI M, TAKAHARA J: Differential gene expression of growth hormone (GH)-releasing hormone (GRH) and GRH receptor in various rat tissues. Endocrinology (1995) 136:4147-4150.
74. HALMOS G, SCHALLY AV, VARGA JL, PLONOWSKI A, REKASI Z, CZOMPOLY T: Human renal cell carcinoma expresses distinct binding sites for growth hormone-releasing hormone. Proc. Natl. Acad. Sci. USA (2000) 97:10555-10560.
75. REKASI Z, CZOMPOLY T, SCHALLY AV, HALMOS G: Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers. Proc. Natl. Acad. Sci. USA (2000) 97:10561-10566.
76. KIARIS H, SCHALLY AV, BUSTO R. HALMOS G, ARTAVANIS-TSAKONAS S, VARGA JL: Expression of splice variant for GHRH receptor SV1 mediates mitogenic effects in 3T3 fibroblasts. Prac. Natl. Acad. Sci. USA (2002) 99: 196-200.
77. KIARIS H, CHATZISTAMOU I, SCHALLY AV et al.: Ligand-dependent and -independent effects of splice variant 1 of growth hormone-releasing hormone receptor. Proc. Natl. Acad. Sci. USA (2003) (In press).
78. SHERWOOD NM, KRUECKL SL, MCRORY JE: The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily. Endocrine Rev. (2000) 21:619-670.
79. MARUNO K, ABSOOD A, SAID SI: Vasoactive intestinal peptide inhibits human small-cell lung cancer proliferation in vitro and in vivo. Proc. Natl. Acad. Sci. USA (1998) 95:14373-14378.
80. REKASI Z, VARGA JL, SCHALLY AV et al.: Antagonists of growth hormone releasing hormone and vasoactive intestinal peptide inhibit tumor proliferation by different mechanisms: evidence from in vitro studies on human prostatic and pancreatic cancers. Endocrinology (2000)
81. PLONOWSKI A, SCHALLY AV, VARGA JL et al: Potentiation of the inhibitory effect of GHRH antagonists on PC-3 human prostate cancer by bombesin antagonists indicative of interference with both IGF and EGF pathways. Prostate (2000) 44:172-180.
82. KIARIS H, SCHALLY AV, VARGA JL, ARMATIS P. Suppression of tumor growth by growth hormone-releasing hormone antagonist JV-1-36 does not involve the inhibition of autocrine production of insulin - like growth Factor II in H-69 small cell lung carcinoma. Cancer Lett. (2000) 161:149-155.
83. GODFREY P, RATHAL JO, BEAMER WG, COPELAND NG, JENKINS NA, MAYO KE. GHRH receptor of little mice contains a missense mutation in the extra-cellular domain that disrupts receptor function. Nat. Genet. (1993) 4:227-232.
84. REKASI Z, SCHALLY AV, PLONOWSKI A, CZOMPOLY T, CSERNUS B, VARGA JL: Regulation of prostate-specific antigen (PSA) gene expression and release in LNCaP prostate cancer by antagonists of growth hormone releasing hormone and vasoactive intestinal peptide. Prostate (2001) 48:188-199.
85. VAUDRY D, GONZALEZ BJ, VASILLE M, YON L, FOURNIER A, VAUDRY H: Pituitary adenyl-cyclase activating polypeptide and its receptors: from structure to functions. Pharmacol. Rev. (2000) 52:269-324.