Adrenomedullin: A tumor progression factor via angiogenic control

Current Cancer Drug Targets

Volumn 6, Issue 7, 2006, Pages 635-643

  Nakamura, Misa ^a,b   Han, Bo ^a   Nunobiki, Osamu ^a   Kakudo, Kennichi ^a  

^a WAKAYAMA MEDICAL UNIVERSITY   (Japan)

^b OSAKA KAWASAKI REHABILITATION UNIVERSITY   (Japan)

Author keywords

Adrenomedullin; Angiogenesis; Hypoxia; Progression; Tumor

Indexed keywords

ADRENOMEDULLIN; ADRENOMEDULLIN RECEPTOR; CALCITONIN GENE RELATED PEPTIDE;

ADRENAL MEDULLA; ANGIOGENESIS; BREAST CANCER; CANCER; CARDIOVASCULAR DISEASE; CENTRAL NERVOUS SYSTEM; DIABETES MELLITUS; ENDOMETRIUM CANCER; ENDOTHELIUM; GENE STRUCTURE; HEART MUSCLE; HUMAN; INFLAMMATION; KIDNEY DISEASE; NEOVASCULARIZATION (PATHOLOGY); OVARY CANCER; PANCREAS CANCER; PHEOCHROMOCYTOMA; PROGNOSIS; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; RNA TRANSLATION; SEPSIS; SIGNAL TRANSDUCTION; TUMOR GROWTH; UTERUS MYOMA; VASCULAR SMOOTH MUSCLE;

ADRENOMEDULLIN; ANIMALS; DISEASE PROGRESSION; ENDOMETRIAL NEOPLASMS; FEMALE; HUMANS; MALE; NEOPLASMS; NEOVASCULARIZATION, PHYSIOLOGIC; OVARIAN NEOPLASMS; PANCREATIC NEOPLASMS; PROGNOSIS; PROSTATIC NEOPLASMS; PROTEIN BIOSYNTHESIS; RECEPTORS, PEPTIDE; SIGNAL TRANSDUCTION;

EID: 33750609353     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/156800906778742442     Document Type: Review

References (111)

1. Wimalawansa, S. J. Amylin, calcitonin gene-related peptide, calcitonin, and adrenomedullin: a peptide superfamily. Crit. Rev. Neurobiol. 1997, 11, 167-239.
2. Kitamura, K.; Kangawa, K.; Kawamoto, M.; Ichiki, Y.; Nakamura, S.; Matsuo, H.; Eto, T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophys. Res. Commun. 1993, 192, 553-560.
3. Ishimitsu, T.; Kojima, M.; Kangawa, K.; Hino, J.; Matsuoka, H.; Kitamura, K.; Eto, T.; Matsuo, H. Genomic structure of human adrenomedullin gene. Biochem. Biophys. Res. Commun. 1994, 203, 631-639.
4. Kitamura, K.; Ichiki, Y.; Tanaka, M.; Kawamoto, M.; Emura, J.; Sakakibara, S.; Kangawa, K.; Matsuo, H.; Eto, T. Immunoreactive adrenomedullin in human plasma. FEBS Lett. 1994, 341, 288-290.
5. Nuki, C.; Kawasaki, H.; Kitamura, K.; Takenaga, M.; Kangawa, K.; Eto, T.; Wada, A. Vasodilator effect of adrenomedullin and calcitonin gene-related peptide receptors in rat mesenteric vascular beds. Biochem. Biophys. Res. Commun. 1993, 196, 245-251.
6. Santiago, J. A.; Garrison, E.; Purnell, W. L.; Smith, R. E.; Champion, H. C.; Coy, D. H.; Murphy, W. A.; Kadowitz, P. J. Comparison of responses to adrenomedullin and adrenomedullin analogs in the mesenteric vascular bed of the cat. Eur. J. Pharmacol. 1995, 272, 115-118.
7. Nossaman, B. D.; Feng, C. J.; Cheng, D. Y.; Dewitt, B. J.; Coy, D. H.; Murphy, W. A.; Kadowitz, P. J. Comparative effects of adrenomedullin, an adrenomedullin analog, and CGRP in the pulmonary vascular bed of the cat and rat. Life Sci. 1995, 56, PL63-PL66.
8. Kanazawa, H.; Kurihara, N.; Hirata, K.; Kudoh, S.; Kawaguchi, T.; Takeda, T. Adrenomedullin, a newly discovered hypotensive peptide, is a potent bronchodilator. Biochem. Biophys. Res. Commun. 1994, 205, 251-254.
9. Ebara, T.; Miura, K.; Okumura, M.; Matsuura, T.; Kim, S.; Yukimura, T.; Iwao, H. Effect of adrenomedullin on renal hemodynamics and functions in dogs. Eur. J. Pharmacol. 1994, 263, 69-73.
10. Samson, W. K.; Murphy, T.; Schell, D. A. A novel vasoactive peptide, adrenomedullin, inhibits pituitary adrenocorticotropin release. Endocrinology 1995, 136, 2349-2352.
11. Yamaguchi, T.; Baba, K.; Doi, Y.; Yano, K. Effect of adrenomedullin on aldosterone secretion by dispersed rat adrenal zone glomerulosa cells. Life Sci. 1995, 56, 379-387.
12. Martinez, A.; Weaver, C.; Lopez, J.; Bhathena, S. J.; Elsasser, T. H.; Miller, M. J.; Moody, T. W.; Unsworth, E. J.; Cuttitta, F. Regulation of insulin secretion and blood glucose metabolism by adrenomedullin. Endocrinology 1996, 137, 2626-2632.
13. Allen, M. A.; Ferguson, A. V. In vitro recordings from area postrema neurons demonstrate responsiveness to adrenomedullin. Am. J. Physiol. 1996, 270, R920-925.
14. Miller, M. J.; Martinez, A.; Unsworth, E. J.; Thiele, C. J.; Moody, T. W.; Elsasser, T.; Cuttitta, F. Adrenomedullin expression in human tumor cell lines. Its potential role as an autocrine growth factor. J. Biol. Chem. 1996, 271, 23345-23351.
15. Withers, D. J.; Coppock, H. A.; Seufferlein, T.; Smith, D. M.; Bloom, S. R.; Rozengurt, E. Adrenomedullin stimulates DNA synthesis and cell proliferation via elevation of cAMP in Swiss 3T3 cells. FEBS Lett. 1996, 378, 83-87.
16. Ishizaka, Y.; Ishizaka, Y.; Tanaka, M.; Kitamura, K.; Kangawa, K.; Minamino, N.; Matsuo, H.; Eto, T. Adrenomedullin stimulates cyclic AMP formation in rat vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 1994, 200, 642-646.
17. McLatchie, L. M.; Fraser, N. J.; Main, M. J.; Wise, A.; Brown, J.; Thompson, N.; Solari, R.; Lee, M. G.; Foord, S. M. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 1998, 393, 333-339.
18. Kamitani, S.; Asakawa, M.; Shimekake, Y.; Kuwasako, K.; Nakahara, K.; Sakata, T. The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells. FEBS Lett. 1999, 448, 111-114.
19. Martinez, A.; Miller, M. J.; Unsworth, E. J.; Siegfried, J. M.; Cuttitta, F. Expression of adrenomedullin in normal human lung and in pulmonary tumors. Endocrinology 1995, 136, 4099-4105.
20. Hata, K.; Takebayashi, Y.; Akiba, S.; Fujiwaki, R.; Iida, K.; Nakayama, K.; Nakayama, S.; Fukumoto, M.; Miyazaki, K. Expression of the adrenomedullin gene in epithelial ovarian cancer. Mol. Hum. Reprod. 2000, 6, 867-872.
21. Rocchi, P.; Boudouresque, F.; Zamora, A. J.; Muracciole, X., Lechevallier, E.; Martin, P. M.; Ouafik, L. Expression of adrenomedullin and peptide amidation activity in human prostate cancer and in human prostate cancer cell lines. Cancer Res. 2001, 61, 1196-1206.
22. Martinez, A.; Vos, M.; Guedez, L.; Kaur, G.; Chen, Z.; Garayoa, M.; Pio, R.; Moody, T.; Stetler-Stevenson, W. G.; Kleinman, H. K.; Cuttitta, F. The effects of adrenomedullin overexpression in breast tumor cells. J. Natl. Cancer Inst. 2002, 94, 1226-1237.
23. Abasolo, I.; Yang, L.; Haleem, R.; Xiao, W.; Pio, R.; Cuttitta, F.; Montuenga, L. M.; Kozlowski, J. M.; Calvo, A.; Wang, Z. Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo. Mol. Cell Endocrinol. 2003, 199, 179-187.
24. Hinson, J. P.; Kapas, S.; Smith, D. M. Adrenomedullin, a multifunctional regulatory peptide. Endocr. Rev. 2000, 21, 138-167.
25. Ishimitsu, T.; Miyata, A.; Matsuoka, H.; Kangawa, K. Transcriptional regulation of human adrenomedullin gene in vascular endothelial cells. Biochem. Biophys. Res. Commun. 1998, 243, 463-470.
26. Chini, E. N.; Choi, E.; Grande, J. P.; Burnett, J. C.; Dousa, T. P. Adrenomedullin suppresses mitogenesis in rat mesangial cells via cAMP pathway. Biochem. Biophys. Res. Commun. 1995, 215, 868-873.
27. Kato, J.; Kitamura, K.; Kangawa, K.; Eto, T. Receptors for adrenomedullin in human vascular endothelial cells. Eur. J. Pharmacol. 1995, 289, 383-385.
28. Kamoi, H.; Kanazawa, H.; Hirata, K.; Kurihara, N.; Yano, Y.; Otani, S. Adrenomedullin inhibits the secretion of cytokine-induced neutrophil chemoattractant, a member of the interleukin-8 family, from rat alveolar macrophages. Biochem. Biophys. Res. Commun. 1995, 211, 1031-1035.
29. Kohno, M.; Kano, H.; Horio, T.; Yokokawa, K.; Yasunari, K.; Takeda, T. Inhibition of endothelin production by adrenomedullin in vascular smooth muscle cells. Hypertension 1995, 25, 1185-1190.
30. 2+ mobilization, in bovine aortic endothelial cells. J. Biol. Chem. 1995, 270, 4412-4417.
31. Ikeda, U.; Kanbe, T.; Shimada, K. Adrenomedullin increases inducible nitric oxide synthase in rat vascular smooth muscle cells stimulated with interleukin-1. Hypertension 1996, 27, 1240-1244.
32. Edwards, R. M.; Trizna, W.; Stack, E.; Aiyar, N. Effect of adrenomedullin on cAMP levels along the rat nephron: comparison with CGRP. Am. J. Physiol. 1996, 271, F895-F899.
33. Coppock, H. A.; Owji, A. A.; Austin, C.; Upton, P. D.; Jackson, M. L.; Gardiner, J. V.; Ghatei, M. A.; Bloom, S. R.; Smith, D. M. Rat-2 fibroblasts express specific adrenomedullin receptors, but not calcitonin- gene-related- peptide receptors, which mediate increased intracellular cAMP and inhibit mitogen-activated protein kinase activity. Biochem. J. 1999, 338, 15-22.
34. Osajima, A.; Uezono, Y.; Tamura, M.; Kitamura, K.; Mutoh, Y.; Ueta, Y.; Kangawa, K.; Kawamura, M.; Eto, T.; Yamashita, H.; Izumi, F.; Takasugi, M.; Kuroiwa, A. Adrenomedullin-sensitive receptors are preferentially expressed in cultured rat mesangial cells. Eur. J. Pharmacol. 1996, 315, 319-325.
35. Hjelmqvist, H.; Keil, R.; Mathai, M.; Hubschle, T.; Gerstberger, R. Vasodilation and glomerular binding of adrenomedullin in rabbit kidney are not CGRP receptor mediated. Am. J. Physiol. 1997, 273, R716-R724.
36. Chini, E. N.; Chini, C. C.; Bolliger, C.; Jougasaki, M.; Grande, J. P.; Burnett, Jr. J. C.; Dousa, T. P. Cytoprotective effects of adrenomedullin in glomerular cell injury: central role of cAMP signaling pathway. Kidney Int. 1997, 52, 917-925.
37. Casey, M. L.; Smith, J.; Alsabrook, G.; MacDonald, P. C. Activation of adenylyl cyclase in human myometrial smooth muscle cells by neuropeptides. J. Clin. Endocrinol. Metab. 1997, 82, 3087-3092.
38. Sato, A.; Canny, B. J.; Autelitano, D. J. Adrenomedullin stimulates cAMP accumulation and inhibits atrial natriuretic peptide gene expression in cardiomyocytes. Biochem. Biophys. Res. Commun. 1997, 230, 311-314.
39. Owada, A.; Nonoguchi, H.; Terada, Y.; Marumo, F.; Tomita, K. Microlocalization and effects of adrenomedullin in nephron segments and in mesangial cells of the rat. Am. J. Physiol. 1997, 272, F691-F697.
40. Abe, K.; Minegishi, T.; Tano, M.; Hirakawa, T.; Tsuchiya, M.; Kangawa, K.; Kojima, M.; Ibuki, Y. Expression and effect of adrenomedullin on rat granulosa cell. Endocrinology 1998, 139, 5263-5266.
41. Nishikimi, T.; Horio, T.; Yoshihara, F.; Nagaya, N.; Matsuo, H.; Kangawa, K. Effect of adrenomedullin on cAMP and cGMP levels in rat cardiac myocytes and nonmyocytes. Eur. J. Pharmacol. 1998, 353, 337-344.
42. Iwasaki, H.; Eguchi, S.; Shichiri, M.; Marumo, F.; Hirata, Y. Adrenomedullin as a novel growth-promoting factor for cultured vascular smooth muscle cells: role of tyrosine kinase-mediated mitogen-activated protein kinase activation. Endocrinology 1998, 139, 3432-3441.
43. Mazzocchi, G.; Rebuffat, P.; Gottardo, G.; Nussdorfer, G. G. Adrenomedullin and calcitonin gene-related peptide inhibit aldosterone secretion in rats, acting via a common receptor. Life Sci. 1996, 58, 839-844.
44. Ikenouchi, H.; Kangawa, K.; Matsuo, H.; Hirata, Y. Negative inotropic effect of adrenomedullin in isolated adult rabbit cardiac ventricular myocytes. Circulation 1997, 95, 2318-2324.
45. Hayakawa, H.; Hirata, Y.; Kakoki, M.; Suzuki, Y.; Nishimatsu, H.; Nagata, D.; Suzuki, E.; Kikuchi, K.; Nagano, T.; Kangawa, K.; Matsuo, H.; Sugimoto, T.; Omata, M. Role of nitric oxide-cGMP pathway in adrenomedullin-induced vasodilation in the rat. Hypertension 1999, 33, 689-693.
46. Xu, Y.; Krukoff, T. L. Adrenomedullin stimulates nitric oxide release from SK-N-SH human neuroblastoma cells by modulating intracellular calcium mobilization. Endocrinology 2005, 146, 2295-2305.
47. Iwasaki, H.; Eguchi, S.; Shichiri, M.; Marumo, F.; Hirata, Y. Down-regulation of adenylate cyclase coupled to adrenomedullin receptor in vascular smooth muscle cells. Eur. J. Pharmacol. 1998, 352, 131-134.
48. Sakai, K.; Saito, K.; Ishizuka, N. Adrenomedullin synergistically interacts with endogenous vasodilators in rats: a possible role of K-ATP channels. Eur. J. Pharmacol. 1998, 359, 151-159.
49. Sugo, S.; Minamino, N.; Shoji, H.; Kangawa, K.; Kitamura, K.; Eto, T.; Matsuo, H. Production and secretion of adrenomedullin from vascular smooth muscle cells: augmented production by tumor necrosis factor-α. Biochem. Biophys. Res. Commun. 1994, 203, 719-726.
50. Sugo, S.; Minamino, N.; Kangawa, K.; Miyamoto, K.; Kitamura, K.; Sakata, J.; Eto, T.; Matsuo, H. Endothelial cells actively synthesize and secrete adrenomedullin. Biochem. Biophys. Res. Commun. 1994, 201, 1160-1166.
51. Xu, Y.; Krukoff, T. L. Adrenomedullin in the rostral ventrolateral medulla inhibits baroreflex controlof heart rate: a role for protein kinase A. Br. J. Pharmacol. 2006, 148, 70-77.
52. Xu, Y.; Krukoff, T. L. Adrenomedullin in the rostral ventrolateral medulla increases arterial pressure and heart rate: roles of glutamate and nitric oxide. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004, 287, R729-R734.
53. Sugo, S.; Minamino, N.; Shoji, H.; Kangawa, K.; Kitamura, K.; Eto, T.; Matsuo, H. Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 1995, 207, 25-32.
54. Isumi, Y.; Shoji, H.; Sugo, S.; Tochimoto, T.; Yoshioka, M.; Kangawa, K.; Matsuo, H.; Minamino, N. Regulation of adrenomedullin production in rat endothelial cells. Endocrinology 1998, 139, 838-846.
55. Shoji, H.; Minamino, N.; Kangawa, K.; Matsuo, H. Endotoxin markedly elevates plasma concentration and gene transcription of adrenomedullin in rat. Biochem. Biophys. Res. Commun. 1995, 215, 531-537.
56. Hirata, Y.; Mitaka, C.; Sato, K.; Nagura, T.; Tsunoda, Y.; Amaha, K.; Marumo, F. Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis. J. Clin. Endocrinol. Metab. 1996, 81, 1449-1453.
57. Nishio, K.; Akai, Y.; Murao, Y.; Doi, N.; Ueda, S.; Tabuse, H.; Miyamoto, S.; Dohi, K.; Minamino, N.; Shoji, H.; Kitamura, K.; Kangawa, K.; Matsuo, H. Increased plasma concentrations of adrenomedullin correlate with relaxation of vascular tone in patients with septic shock. Crit. Care Med. 1997, 25, 953-957.
58. Udono, T.; Takahashi, K.; Nakayama, M.; Yoshinoya, A.; Totsune, K.; Murakami, O.; Durlu, Y. K.; Tamai, M.; Shibahara, S. Induction of adrenomedullin by hypoxia in cultured retinal pigment epithelial cells. Invest. Ophthal. Vis. Sci. 2001, 42, 1080-1086.
59. Parameswaran, N.; Spielman, W. S.; Pullen, M.; Francis, J.; Brooks, D. P.; Nambi, P. Mechanism of adrenomedullin-stimulated hyaluronic acid release in rat mesangialcells. Eur. J. Pharmacol. 1999, 16, 313-318.
60. Caron, K. M.; Smithies, O. Extreme hydrops fetalis and cardiovascular abnormalities in mice lacking a functional adrenomedullin gene. Proc. Natl. Acad. Sci. USA 2001, 98, 615-619.
61. Shindo, T.; Kurihara, Y.; Nishimatsu, H.; Moriyama, N.; Kakoki, M.; Wang, Y.; Imai, Y.; Ebihara, A.; Kuwaki, T.; Ju, K. H.; Minamino, N.; Kangawa, K.; Ishikawa, T.; Fukuda, M.; Akimoto, Y.; Kawakami, H.; Imai, T.; Morita, H.; Yazaki, Y.; Nagai, R.; Hirata, Y.; Kurihara H. Vascular abnormalities and elevated blood pressure in mice lacking adrenomedullin gene. Circulation 2001, 16, 1964-1971.
62. Bonanno, E.; Iurlaro, M.; Madri, J. A.; Nicosia, R. F. Type IV collagen modulates angiogenesis and neovessel survival in the rat aorta model. In vitro Cell Dev. Biol. Anim. 2000, 36, 336-340.
63. Hata, K.; Takebayashi, Y.; Akiba, S.; Fujiwaki, R.; Iida, K.; Nakayama, K.; Nakayama, S.; Fukumoto, M.; Miyazaki, K. Expression of the adrenomedullin gene in epithelial ovarian cancer. Mol. Hum. Reprod. 2000, 6, 8678-8672.
64. Letizia, C.; De Toma, G.; Cerci, S.; Massa, R.; Coassin, S.; Subioli, S.; Scuro, L.; De Ciocchis, A. Adrenomedullin levels are high in primary aldosteronism due to adenoma and decline after surgical cure. Blood Press. 1998, 7, 19-23.
65. Oehler, M. K.; Hague, S.; Rees, M. C.; Bicknell, R. Adrenomedullin promotes formation of xenografted endometrial tumors by stimulation of autocrine growth and angiogenesis. Oncogene 2002, 21, 2815-2821.
66. Oehler, M. K.; Fischer, D. C.; Orlowska-Volk, M.; Herrle, F.; Kieback, D. G.; Rees, M. C.; Bicknell, R. Tissue and plasma expression of the angiogenic peptide adrenomedullin in breast cancer. Br. J. Cancer 2003, 89, 1927-1933.
67. Cormier-Regard, S.; Nguyen, S. V.; Claycomb, W. C. Adrenomedullin gene expression is developmentally regulated and induced by hypoxia in rat ventricular cardiac myocytes. J. Biol. Chem. 1998, 273, 17787-17792.
68. Garayoa, M.; Martinez, A.; Lee, S.; Pio, R.; An, W. G.; Neckers, L.; Trepel, J.; Montuenga, L. M.; Ryan, H.; Johnson, R.; Gassmann, M.; Cuttitta, F. Hypoxia-inducible factor-1 (HIF-1) up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation: a possible promotion mechanism of carcinogenesis. Mol. Endocrinol. 2000, 14, 848-862.
69. Niizeki, H.; Kobayashi, M.; Horiuchi, I.; Akakura, N.; Chen, J.; Wang, J.; Hamada, J. I.; Seth, P.; Katoh, H.; Watanabe, H.; Raz, A.; Hosokawa, M. Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells. Br. J. Cancer 2002, 86, 1914-1919.
70. Cuttitta, F.; Pio, R.; Garayoa, M.; Zudaire, E.; Julian, M.; Elsasser, T. H.; Montuenga, L. M.; Martinez, A. Adrenomedullin functions as an important tumor survival factor in human carcinogenesis. Microsc. Res. Tech. 2002, 57, 110-119.
71. Shweiki, D.; Itin, A.; Neufeld, G.; Gitay-Goren, H.; Keshet, E. Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J. Clin. Invest. 1993, 91, 2235-2243.
72. Zhang, L.; Rees, M. C.; Bicknell, R. The isolation and long-term culture of normal human endometrial epithelium and stroma. Expression of mRNAs for angiogenic polypeptides basally and on oestrogen and progesterone challenges. J. Cell Sci. 1995, 108, 323-331.
73. Zhao, Y.; Hague, S.; Manek, S.; Zhang, L.; Bicknell, R.; Rees, M. C. PCR display identifies tamoxifen induction of the novel angiogenic factor adrenomedullin by a non estrogenic mechanism in the human endometrium. Oncogene 1998, 16, 409-415.
74. Iimuro, S.; Shindo, T.; Moriyama, N.; Amaki, T.; Niu, P.; Takeda, N.; Iwata, H.; Zhang, Y.; Ebihara, A.; Nagai, R. Angiogenic effects of adrenomedullin in ischemia and tumor growth. Circ. Res. 2004, 20, 415-423.
75. Hague, S.; Zhang, L.; Oehler, M. K.; Manek, S.; MacKenzie, I. Z.; Bicknell, R.; Rees, M. C. Expression of the hypoxically regulated angiogenic factor adrenomedullin correlates with uterine leiomyoma vascular density. Clin. Cancer Res. 2000, 6, 2808-2814.
76. Oehler, M. K.; Norbury, C.; Hague, S.; Rees, M. C.; Bicknell, R. Adrenomedullin inhibits hypoxic cell death by upregulation of Bcl-2 in endometrial cancer cells: a possible promotion mechanism for tumour growth. Oncogene 2001, 24, 2937-2945.
77. Martinez, A.; Vos, M.; Guedez, L.; Kaur, G.; Chen, Z.; Garayoa, M., Pio, R.; Moody, T.; Stetler-Stevenson, W. G.; Kleinman, H. K.; Cuttitta, F. The effects of adrenomedullin overexpression in breast tumor cells. J. Natl. Cancer Inst. 2002, 94, 1226-1237.
78. Ishikawa, T.; Chen, J.; Wang, J.; Okada, F.; Sugiyama, T.; Kobayashi, T.; Shindo, M.; Higashino, F.; Katoh, H.; Asaka, M.; Kondo, T.; Hosokawa, M.; Kobayashi, M. Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by suppressing angiogenesis. Oncogene 2003, 22, 1238-1242.
79. Ouafik, L.; Sauze, S.; Boudouresque, F.; Chinot, O.; Delfino, C.; Fina, F.; Vuaroqueaux, V.; Dussert, C.; Palmari, J.; Dufour, H.; Grisoli, F.; Casellas, P; Brunner, N.; Martin, P. M. Neutralization of adrenomedullin inhibits the growth of human glioblastoma cell lines in vitro and suppresses tumor xenograft growth in vivo. Am. J. Pathol. 2002, 160, 1279-1292.
80. Iwase, T.; Nagaya, N.; Fujii, T.; Itoh, T.; Ishibashi-Ueda, H.; Yamagishi, M.; Miyatake, K.; Matsumoto, T.; Kitamura, S.; Kangawa, K. Adrenomedullin enhances angiogenic potency of bone marrow transplantation in a rat model of hindlimb ischemia. Circulation 2005, 111, 356-362.
81. Nikitenko, L. L.; MacKenzie, I. Z.; Rees, M. C.; Bicknell, R. Adrenomedullin is an autocrine regulator of endothelial growth in human endometrium. Mol. Hum. Reprod. 2000, 6, 811-819.
82. White, I. N. The tamoxifen dilemma. Carcinogenesis 1999, 20, 1153-1160.
83. Bergman, L.; Beelen, M. L.; Gallee, M. P.; Hollema, H.; Benraadt, J.; van Leeuwen, F. E. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of liver and endometrial cancer risk following tamoxifen. Lancet 2000, 356, 881-887.
84. Hague, S.; Manek, S.; Oehler, M. K.; MacKenzie, I. Z.; Bicknell, R.; Rees, M. C. Tamoxifen induction of angiogenic factor expression in endometrium. Br. J. Cancer 2002, 86, 761-767.
85. Webb, P.; Lopez, G. N.; Uht, R. M.; Kushner, P. J. Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. Mol. Endocrinol. 1995, 9, 443-456.
86. Miseki, T.; Kawakami, H.; Natsuizaka, M.; Darmanin, S.; Cui, H. Y.; Chen, J.; Fu, Q.; Okada, F.; Shindo, M.; Higashino, F.; Asaka, M.; Hamuro, J.; Kobayashi, M. Suppression of tumor growth by intra-muscular transfer of naked DNA encoding adrenomedullin antagonist. Cancer Gene Ther. 2006, (in press)
87. Akakura, N.; Kobayashi, M.; Horiuchi, I.; Suzuki, A.; Wang, J.; Chen, J.; Niizeki, H.; Kawamura, K.; Hosokawa, M.; Asaka, M. Constitutive expression of hypoxia- inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation. Cancer Res. 2001, 61, 6548-6554.
88. Kato, H.; Shichiri, M.; Marumo, F.; Hirata, Y. Adrenomedullin as an autocrine/paracrine apoptosis survival factor for rat endothelial cells. Endocrinology 1997, 138, 2615-2620.
89. Carmeliet, P.; Jain, R. K. Angiogenesis in cancer and other diseases. Nature 2000, 407, 249-257.
90. Folkman, J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. 1995, 1, 27-31.
91. Browder, T.; Folkman, J.; Pirie-Shepherd, S. The hemostatic system as a regulator of angiogenesis. J. Biol. Chem. 2000, 275, 1521-1524.
92. Carmeliet, P. VEGF gene therapy: stimulating angiogenesis or angioma-genesis? Nat. Med. 2000, 6, 1102-1103.
93. Kerbel, R. S. Tumor angiogenesis: past, present and the near future. Carcinogenesis 2000, 21, 505-515.
94. Drake, C. J.; Little, C. D. Exogenous vascular endothelial growth factor induces malformed and hyperfused vessels during embryonic neovascularization. Proc. Natl. Acad. Sci. USA 1995, 92, 7657-7661.
95. Suri, C.; McClain, J.; Thurston, G.; McDonald, D. M.; Zhou, H.; Oldmixon, E. H.; Sato, T .N.; Yancopoulos, G. D. Increased vascularization in mice overexpressing angiopoietin-1. Science 1998, 282, 468-471.
96. Carmeliet, P.; Dor, Y.; Herbert, J. M.; Fukumura, D.; Brusselmans, K.; Dewerchin, M.; Neeman, M.; Bono, F.; Abramovitch, R.; Maxwell, P.; Koch, C. J.; Ratcliffe, P.; Moons, L.; Jain, R. K.; Collen, D.; Keshert, E. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 1998, 394, 485-490.
97. Cohen, R. J.; Glezerson, G.; Haffejee, Z. Neuro-endocrine cells - a new prognostic parameter in prostate cancer. Br. J. Urol. 1991, 68, 258-262.
98. Abrahamsson, P. A.; Falkmer, S.; Falt, K.; Grimelius, L. The course of neuroendocrine differentiation in prostatic carcinomas. An immunohistochemical study testing chromogranin A as an "endocrine marker". Pathol. Res. Pract. 1989, 185, 373-380.
99. Tetu, B.; Katz, R. L.; Kalter, S. P.; von Eschenbach, A. C.; Barlogie, B. Acridine-orange flow cytometry of urinary bladder washings for the detection of transitional cell carcinoma of the bladder. The influence of prior local therapy. Cancer 1987, 60, 1815-1822.
100. Jimenez, N.; Calvo, A.; Martinez, A.; Rosell, D.; Cuttitta, F.; Montuenga, L. M. Expression of adrenomedullin and proadrenomedullin N-terminal 20 peptide in human and rat prostate. J. Histochem. Cytochem. 1999, 47, 1167-1178.
101. Shimosawa, T.; Ito, Y.; Ando, K.; Kitamura, K.; Kangawa, K.; Fujita, T. Proadrenomedullin NH (2)-terminal 20 peptide, a new product of the adrenomedullin gene, inhibits norepinephrine overflow from nerve endings. J. Clin. Invest. 1995, 96, 1672-1676.
102. Samson, W. K.; Murphy, T. C.; Resch, Z. T. Proadrenomedullin N-terminal 20 peptide inhibits adrenocorticotropin secretion from cultured pituitary cells, possibly via activation of a potassium channel. Endocrine 1998, 9, 269-272.
103. Ando, K.; Omi, N.; Shimosawa, T.; Fujita, T. Proadrenomedullin N-terminal 20 peptide (PAMP) inhibits proliferation of human neuroblastoma TGW cells. FEBS Lett. 1997, 413, 462-466.
104. Jimenez, N.; Jongsma, J.; Calvo, A.; van der Kwast, T. H.; Treston, A. M.; Cuttitta, F.; Schroder, F. H.; Montuenga, L. M.; van Steenbrugge, G. J. Peptidylglycine alpha-amidating monooxygenase- and proadrenomedullin- derived peptide-associated neuroendocrine differentiation are induced by androgen deprivation in the neoplastic prostate. Int. J. Cancer 2001, 94, 28-34.
105. Abasolo, I.; Wang, Z.; Montuenga, L. M.; Calvo, A. Adrenomedullin inhibits prostate cancer cell proliferation through a cAMP-independent autocrine mechanism. Biochem. Biophys. Res. Commun. 2004, 24, 878-886.
106. Giacalone, P. L.; Daures, J. P.; Ouafik, L.; Martin, P. M.; Laffargue, F.; Maudelonde, T. Steroids and adrenomedullin growth patterns in human ovarian cancer cells: estrogenic-regulation assay. Gynecol. Oncol. 2003, 91, 651-656.
107. Giacalone, P. L.; Vuaroqueaux, V.; Daures, J. P.; Houafic, L.; Martin, P. M.; Laffargue, F.; Maudelonde, T. Expression of adrenomedullin in human ovaries, ovarian cysts and cancers. Correlation with estrogens receptor status. Eur. J. Obstet. Gynecol. Reprod. Biol. 2003, 110, 224-229.
108. Letizia, C.; De Toma, G.; Caliumi, C.; Cerci, S.; Massa, R.; Loria, R. D.; Alo, P.; Marinoni, E. M.; Diacinti, D.; D'Erasmo, E. Plasma adrenomedullin concentrations in patients with adrenal pheochromocytoma. Horm. Metab. Res. 2001, 33, 290-294.
109. Zudaire, E.; Martinez, A.; Garayoa, M.; Pio, R.; Kaur, G.; Woolhiser, M. R.; Metcalfe, D. D.; Hook, W. A.; Siraganian, R. P.; Guise, T. A.; Chirgwin, J. M.; Cuttitta, F. Adrenomedullin is a cross-talk molecule that regulates tumor and mast cell function during human carcinogenesis. Am. J. Pathol. 2006, 168, 280-291.
110. 2-terminal 20 peptide is a potent angiogenic factor, and its inhibition results in reduction of tumor growth. Cancer Res. 2004, 15, 6489-6494.
111. Beltowski, J.; Jamroz, A. Adrenomedullin - what do we know 10 years since its discovery? Pol. J. Pharmacol. 2004, 56, 5-27.