The biological hallmarks of ileal carcinoids

European Journal of Clinical Investigation

Volumn 41, Issue 12, 2011, Pages 1353-1360

  Cunningham, Janet L ^a   Janson, Eva T ^a  

^a UPPSALA UNIVERSITY   (Sweden)

Author keywords

Carcinoid syndrome; Midgut carcinoid; Neuroendocrine tumour; Serotonin; Small intestine; Tumour biology; Well differentiated endocrine carcinoma

Indexed keywords

APOLIPOPROTEIN; B RAF KINASE; BETA CATENIN; K RAS PROTEIN; KI 67 ANTIGEN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE; OCTREOTIDE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN P53; RAPAMYCIN; RECOMBINANT TRANSFORMING GROWTH FACTOR BETA1; SEROTONIN; SMAD7 PROTEIN; SOMATOMEDIN C; TACHYKININ; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR HOXC6; TRANSFORMING GROWTH FACTOR ALPHA; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; TRANSFORMING GROWTH FACTOR BETA3; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; WNT PROTEIN;

ANGIOGENESIS; ANTIGEN EXPRESSION; APOPTOSIS; CANCER GROWTH; CARCINOGENESIS; CARCINOID; CELL CYCLE; CELL PROLIFERATION; CLINICAL FEATURE; DISEASE SEVERITY; ENTEROCHROMAFFIN CELL; GENE MUTATION; HORMONE RELEASE; HUMAN; ILEAL CARCINOID; ILEUM CANCER; INTESTINE CRYPT; INTRACELLULAR SIGNALING; METASTASIS; MITOSIS; NICK END LABELING; ONCOGENE C MYC; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; REVIEW; STROMA; SYMPTOMATOLOGY; UNSPECIFIED SIDE EFFECT; VASCULARIZATION;

CARCINOID TUMOR; HUMANS; ILEAL NEOPLASMS; SEROTONIN; TACHYKININS; TUMOR MARKERS, BIOLOGICAL;

EID: 81355149896     PISSN: 00142972     EISSN: 13652362     Source Type: Journal    
DOI: 10.1111/j.1365-2362.2011.02537.x     Document Type: Review

References (81)

1. Kloppel G, Perren A, Heitz PU. The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci 2004;1014:13-27.
2. Duerr E, Mizukami Y, Warshaw A, Kulke M, Chung C. Gene expression profiles of pancreatic neuroendocrine tumors and gastrointestinal carcinoids. Gastroenterology 2006;130(Suppl. 2):S1887.
3. D'Adda T, Pizzi S, Azzoni C, Bottarelli L, Crafa P, Pasquali C et al. Different patterns of 11q allelic losses in digestive endocrine tumors. Hum Pathol 2002;33:322-9.
4. Kytola S, Hoog A, Nord B, Cedermark B, Frisk T, Larsson C et al. Comparative genomic hybridization identifies loss of 18q22-qter as an early and specific event in tumorigenesis of midgut carcinoids. Am J Pathol 2001;158:1803-8.
5. Löllgen RM, Hessman O, Szabo E, Westin G, Åkerström G. Chromosome 18 deletions are common events in classical midgut carcinoid tumors. Int J Cancer 2001;92:812-5.
6. Moertel CG. Karnofsky memorial lecture. An odyssey in the land of small tumors. J Clin Oncol 1987;5:1502-22.
7. Cunningham JL, Janson ET, Agarwal S, Grimelius L, Stridsberg M. Tachykinins in endocrine tumors and the carcinoid syndrome. Eur J Endocrinol 2008;159:275-82.
8. Öberg K, Ferone D, Kaltsas G, Knigge UP, Taal B, Plockinger U. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biotherapy. Neuroendocrinology 2009;90:209-13.
9. Janson ET, Sorbye H, Welin S, Federspiel B, Gronbaek H, Hellman P et al. Nordic Guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours. Acta Oncol 2010;49:740-56.
10. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70.
11. Cunningham JL, Grimelius L, Sundin A, Agarwal S, Janson ET. Malignant ileocaecal serotonin-producing carcinoid tumours: the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis. Acta Oncol 2007;46:747-56.
12. Canavese G, Azzoni C, Pizzi S, Corleto VD, Pasquali C, Davoli C et al. p27: a potential main inhibitor of cell proliferation in digestive endocrine tumors but not a marker of benign behavior. Hum Pathol 2001;32:1094-101.
13. Tannapfel A, Vomschloss S, Karhoff D, Markwarth A, Hengge UR, Wittekind C et al. BRAF gene mutations are rare events in gastroenteropancreatic neuroendocrine tumors. Am J Clin Pathol 2005;123:256-60.
14. Weckström P, Hedrum A, Makridis C, Åkerström G, Rastad J, Scheibenpflug L et al. Midgut carcinoids and solid carcinomas of the intestine: differences in endocrine markers and p53 mutations. Endocr Pathol 1996;7:273-9.
15. Paraskevakou H, Saetta A, Skandalis K, Tseleni S, Athanassiadis A, Davaris PS. Morphological-histochemical study of intestinal carcinoids and K-ras mutation analysis in appendiceal carcinoids. Pathol Oncol Res 1999;5:205-10.
16. Pizzi S, Azzoni C, Bassi D, Bottarelli L, Milione M, Bordi C. Genetic alterations in poorly differentiated endocrine carcinomas of the gastrointestinal tract. Cancer 2003;98:1273-82.
17. Ramnani DM, Wistuba II, Behrens C, Gazdar AF, Sobin LH, Albores-Saavedra J K-ras and p53 mutations in the pathogenesis of classical and goblet cell carcinoids of the appendix. Cancer 1999;86:14-21.
18. Yashiro T, Fulton N, Hara H, Yasuda K, Montag A, Yashiro N et al. Comparison of mutations of ras oncogene in human pancreatic exocrine and endocrine tumors. Surgery 1993;114:758-63; discussion 63-4.
19. Yoshimoto K, Iwahana H, Fukuda A, Sano T, Saito S, Itakura M. Role of p53 mutations in endocrine tumorigenesis: mutation detection by polymerase chain reaction-single strand conformation polymorphism. Cancer Res 1992;52:5061-4.
20. Wimmel A, Wiedenmann B, Rosewicz S. Autocrine growth inhibition by transforming growth factor beta-1 (TGFbeta-1) in human neuroendocrine tumour cells. Gut 2003;52:1308-16.
21. Kidd M, Modlin IM, Pfragner R, Eick GN, Champaneria MC, Chan AK et al. Small bowel carcinoid (enterochromaffin cell) neoplasia exhibits transforming growth factor-beta1-mediated regulatory abnormalities including up-regulation of C-Myc and MTA1. Cancer 2007;109:2420-31.
22. Shah T, Hochhauser D, Frow R, Quaglia A, Dhillon AP, Caplin ME. Epidermal growth factor receptor expression and activation in neuroendocrine tumours. J Neuroendocrinol 2006;18:355-60.
23. Arvidsson Y, Andersson E, Bergstrom A, Andersson MK, Altiparmak G, Illerskog AC et al. Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract. Endocr Relat Cancer 2008;15:569-81.
24. Kunnimalaiyaan M, Yan S, Wong F, Zhang YW, Chen H. Hairy Enhancer of Split-1 (HES-1), a Notch1 effector, inhibits the growth of carcinoid tumor cells. Surgery 2005;138:1137-42; discussion 42.
25. Kunnimalaiyaan M, Traeger K, Chen H. Conservation of the Notch1 signaling pathway in gastrointestinal carcinoid cells. Am J Physiol Gastrointest Liver Physiol 2005;289:G636-42.
26. Fujiki K, Duerr EM, Kikuchi H, Ng A, Xavier RJ, Mizukami Y et al. Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology 2008;135:907-16, 16 e1-2.
27. Ramachandran S, Liu P, Young AN, Yin-Goen Q, Lim SD, Laycock N et al. Loss of HOXC6 expression induces apoptosis in prostate cancer cells. Oncogene 2005;24:188-98.
28. Kulke MH, Lenz HJ, Meropol NJ, Posey J, Ryan DP, Picus J et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol 2008;26:3403-10.
29. Toliat MR, Berger W, Ropers HH, Neuhaus P, Wiedenmann B. Mutations in the MEN I gene in sporadic neuroendocrine tumours of gastroenteropancreatic system. Lancet 1997;350:1223.
30. Gortz B, Roth J, Krahenmann A, de Krijger RR, Muletta-Feurer S, Rutimann K et al. Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. Am J Pathol 1999;154:429-36.
31. Pai VP, Marshall AM, Hernandez LL, Buckley AR, Horseman ND. Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival. Breast Cancer Res 2009;11:R81.
32. Vikman S, Essand M, Cunningham JL, de la Torre M, Oberg K, Totterman TH et al. Gene expression in midgut carcinoid tumors: potential targets for immunotherapy. Acta Oncol 2005;44:32-40.
33. Ishizuka J, Beauchamp RD, Townsend CM Jr, Greeley GH Jr, Thompson JC Receptor-mediated autocrine growth-stimulatory effect of 5-hydroxytryptamine on cultured human pancreatic carcinoid cells. J Cell Physiol 1992;150:1-7.
34. Svejda B, Kidd M, Giovinazzo F, Eltawil K, Gustafsson BI, Pfragner R et al. The 5-HT(2B) receptor plays a key regulatory role in both neuroendocrine tumor cell proliferation and the modulation of the fibroblast component of the neoplastic microenvironment. Cancer 2010;116:2902-12.
35. Welin S, Fjällskog ML, Saras J, Eriksson B, Janson ET. Expression of tyrosine kinase receptors in malignant midgut carcinoid tumors. Neuroendocrinology 2006;84:42-8.
36. Wulbrand U, Wied M, Zofel P, Goke B, Arnold R, Fehmann H. Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours. Eur J Clin Invest 1998;28:1038-49.
37. Wulbrand U, Remmert G, Zofel P, Wied M, Arnold R, Fehmann HC. mRNA expression patterns of insulin-like growth factor system components in human neuroendocrine tumours. Eur J Clin Invest 2000;30:729-39.
38. Nilsson O, Wangberg B, McRae A, Dahlström A, Ahlman H. Growth factors and carcinoid tumours. Acta Oncol 1993;32:115-24.
39. Zhang PJ, Furth EE, Cai X, Goldblum JR, Pasha TL, Min KW. The role of beta-catenin, TGF beta 3, NGF2, FGF2, IGFR2, and BMP4 in the pathogenesis of mesenteric sclerosis and angiopathy in midgut carcinoids. Hum Pathol 2004;35:670-4.
40. Krishnamurthy S, Dayal Y. Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in gastrointestinal carcinoids. Am J Surg Pathol 1997;21:327-33.
41. Kaltsas G, Cunningham J, Falkmer S, Grimelius L, Tsolakis A. Expression of connective tissue growth factor and insulin growth factor 1 in normal and neoplastic gastrointestinal neuroendocrine cells and their clinicopathological significance. Endocr Relat Cancer 2010;18:61-71.
42. von Wichert G, Jehle PM, Hoeflich A, Koschnick S, Dralle H, Wolf E et al. Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. Cancer Res 2000;60:4573-81.
43. Pitt SC, Davis R, Kunnimalaiyaan M, Chen H. AKT and PTEN expression in human gastrointestinal carcinoid tumors. Am J Transl Res 2009;1:291-9.
44. Leu FP, Nandi M, Niu C. The effect of transforming growth factor beta on human neuroendocrine tumor BON cell proliferation and differentiation is mediated through somatostatin signaling. Mol Cancer Res 2008;6:1029-42.
45. Rinke A, Muller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 2009;27:4656-63.
46. Pavel M, Hainsworth J, Baudin E, Peeters E, Hoersch D, Anthony L et al. A randomized, double-blind, placebo-controlled, multicenter phase III trial of everolimus + octreotide lar vs placebo + octreotide lar in patients with advanced neuroendocrine tumors (net) (radiant-2). 35th ESMO Congress, Milan; 2010.
47. Zitzmann K, Ruden JV, Brand S, Goke B, Lichtl J, Spottl G et al. Compensatory activation of Akt in response to mTOR and Raf inhibitors - a rationale for dual-targeted therapy approaches in neuroendocrine tumor disease. Cancer Lett 2010;295:100-9.
48. Cerovac V, Monteserin-Garcia J, Rubinfeld H, Buchfelder M, Losa M, Florio T et al. The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells. Cancer Res 2010;70:666-74.
49. Cunningham JL, Diaz De Stahl T, Sjöblom T, Westin G, Dumanski JP, Janson ET. Common pathogenetic mechanism involving human chromosome 18 in familial and sporadic ileal carcinoid tumors. Genes Chromosom Cancer 2011;50:82-94.
50. La Rosa S, Uccella S, Finzi G, Albarello L, Sessa F, Capella C. Localization of vascular endothelial growth factor and its receptors in digestive endocrine tumors: correlation with microvessel density and clinicopathologic features. Hum Pathol 2003;34:18-27.
51. Besig S, Voland P, Baur DM, Perren A, Prinz C. Vascular endothelial growth factors, angiogenesis, and survival in human ileal enterochromaffin cell carcinoids. Neuroendocrinology 2009;90:402-15.
52. Druce M, Rockall A, Grossman AB. Fibrosis and carcinoid syndrome: from causation to future therapy. Nat Rev Endocrinol 2009;5:276-83.
53. Yen TH, Wright NA. The gastrointestinal tract stem cell niche. Stem Cell Rev 2006;2:203-12.
54. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009;459:262-5.
55. Cunningham JL, Tsolakis A, Jacobson A, Janson E. Connective tissue growth factor (CTGF) expression in endocrine tumors is associated with high stromal expression of alpha-smooth muscle actin. Eur J Endocrinol 2010;163:691-7.
56. Su MC, Wang CC, Chen CC, Hu RH, Wang TH, Kao HL et al. Nuclear translocation of beta-catenin protein but absence of beta-catenin and APC mutation in gastrointestinal carcinoid tumor. Ann Surg Oncol 2006;13:1604-9.
57. Zhang HY, Rumilla KM, Jin L, Nakamura N, Stilling GA, Ruebel KH et al. Association of DNA methylation and epigenetic inactivation of RASSF1A and beta-catenin with metastasis in small bowel carcinoid tumors. Endocrine 2006;30:299-306.
58. Grotendorst GR, Okochi H, Hayashi N. A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene. Cell Growth Differ 1996;7:469-80.
59. Duncan MR, Frazier KS, Abramson S, Williams S, Klapper H, Huang X et al. Connective tissue growth factor mediates transforming growth factor beta-induced collagen synthesis: down-regulation by cAMP. FASEB J 1999;13:1774-86.
60. Weston BS, Wahab NA, Mason RM. CTGF mediates TGF-beta-induced fibronectin matrix deposition by upregulating active alpha5beta1 integrin in human mesangial cells. J Am Soc Nephrol 2003;14:601-10.
61. Rachfal AW, Brigstock DR. Connective tissue growth factor (CTGF/CCN2) in hepatic fibrosis. Hepatol Res 2003;26:1-9.
62. Secker GA, Shortt AJ, Sampson E, Schwarz QP, Schultz GS, Daniels JT. TGFbeta stimulated re-epithelialisation is regulated by CTGF and Ras/MEK/ERK signalling. Exp Cell Res 2008;314:131-42.
63. Liu XC, Liu BC, Zhang XL, Li MX, Zhang JD. Role of ERK1/2 and PI3-K in the regulation of CTGF-induced ILK expression in HK-2 cells. Clin Chim Acta 2007;382:89-94.
64. Kidd M, Modlin IM, Shapiro MD, Camp RL, Mane SM, Usinger W et al. CTGF, intestinal stellate cells and carcinoid fibrogenesis. World J Gastroenterol 2007;13:5208-16.
65. Brigstock DR, Steffen CL, Kim GY, Vegunta RK, Diehl JR, Harding PA. Purification and characterization of novel heparin-binding growth factors in uterine secretory fluids. Identification as heparin-regulated Mr 10, 000 forms of connective tissue growth factor. J Biol Chem 1997;272:20275-82.
66. Imam H, Eriksson B, Lukinius A, Janson ET, Lindgren PG, Wilander E et al. Induction of apoptosis in neuroendocrine tumors of the digestive system during treatment with somatostatin analogs. Acta Oncol 1997;36:607-14.
67. Welin SV, Janson ET, Sundin A, Stridsberg M, Lavenius E, Granberg D et al. High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours. Eur J Endocrinol 2004;151:107-12.
68. Wahab N, Cox D, Witherden A, Mason RM. Connective tissue growth factor (CTGF) promotes activated mesangial cell survival via up-regulation of mitogen-activated protein kinase phosphatase-1 (MKP-1). Biochem J 2007;406:131-8.
69. Drozdov I, Kidd M, Nadler B, Camp RL, Mane SM, Hauso O et al. Predicting neuroendocrine tumor (carcinoid) neoplasia using gene expression profiling and supervised machine learning. Cancer 2009;115:1638-50.
70. Kulke MH, Freed E, Chiang DY, Philips J, Zahrieh D, Glickman JN et al. High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. Genes Chromosom Cancer 2008;47:591-603.
71. Lee BY, Han JA, Im JS, Morrone A, Johung K, Goodwin EC et al. Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell 2006;5:187-95.
72. Shay JW, Roninson IB. Hallmarks of senescence in carcinogenesis and cancer therapy. Oncogene 2004;23:2919-33.
73. Lubomierski N, Kersting M, Bert T, Muench K, Wulbrand U, Schuermann M et al. Tumor suppressor genes in the 9p21 gene cluster are selective targets of inactivation in neuroendocrine gastroenteropancreatic tumors. Cancer Res 2001;61:5905-10.
74. Liu L, Broaddus RR, Yao JC, Xie S, White JA, Wu TT et al. Epigenetic alterations in neuroendocrine tumors: methylation of RAS-association domain family 1, isoform A and p16 genes are associated with metastasis. Mod Pathol 2005;18:1632-40.
75. Kidd M, Eick G, Shapiro MD, Camp RL, Mane SM, Modlin IM. Microsatellite instability and gene mutations in transforming growth factor-beta type II receptor are absent in small bowel carcinoid tumors. Cancer 2005;103:229-36.
76. Ghimenti C, Tannergard P, Wahlberg S, Liu T, Giulianotti PG, Mosca F et al. Microsatellite instability and mismatch repair gene inactivation in sporadic pancreatic and colon tumours. Br J Cancer 1999;80:11-6.
77. Leja J, Essaghir A, Essand M, Wester K, Oberg K, Totterman TH et al. Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Mod Pathol 2009;22:261-72.
78. Schwarze SR, Luo J, Isaacs WB, Jarrard DF. Modulation of CXCL14 (BRAK) expression in prostate cancer. Prostate 2005;64:67-74.
79. Ozawa S, Kato Y, Komori R, Maehata Y, Kubota E, Hata R. BRAK/CXCL14 expression suppresses tumor growth in vivo in human oral carcinoma cells. Biochem Biophys Res Commun 2006;348:406-12.
80. Ruebel K, Leontovich AA, Stilling GA, Zhang S, Righi A, Jin L et al. MicroRNA expression in ileal carcinoid tumors: downregulation of microRNA-133a with tumor progression. Mod Pathol 2010;23:367-75.
81. Duisters RF, Tijsen AJ, Schroen B, Leenders JJ, Lentink V, van der Made I et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodelling. Circ Res 2009;104:170-8.