Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors.

Szczegóły
Abstrakt

Tytuł:: Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors.
Autorzy:: Sampedro-Núñez M; Department of Endocrinology and Nutrition, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain.
Luque RM; Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba 14014, Spain.
Ramos-Levi AM; Department of Endocrinology and Nutrition, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain.
Gahete MD; Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba 14014, Spain.
Serrano-Somavilla A; Department of Endocrinology and Nutrition, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain.
Villa-Osaba A; Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba 14014, Spain.
Adrados M; Department of Endocrinology and Nutrition, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain.
Ibáñez-Costa A; Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba 14014, Spain.
Martín-Pérez E; Department of Endocrinology and Nutrition, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain.
Culler MD; IPSEN Bioscience, Cambridge, Massachusetts 02142, USA.
Marazuela M; Department of Endocrinology and Nutrition, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Universidad Autónoma de Madrid, Madrid 28006, Spain.
Castaño JP; Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, and CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba 14014, Spain.
Źródło:: Oncotarget [Oncotarget] 2016 Feb 09; Vol. 7 (6), pp. 6593-608.
Typ publikacji:: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Albany, N.Y. : Impact Journals
MeSH Terms:: Angiogenic Proteins/*genetics
Neoplasm Recurrence, Local/*pathology
Neuroendocrine Tumors/*pathology
Pancreatic Neoplasms/*pathology
RNA Splicing/*genetics
Receptors, Somatostatin/*genetics
Adult ; Aged ; Aged, 80 and over ; Angiogenic Proteins/metabolism ; Apoptosis ; Cell Movement ; Cell Proliferation ; Female ; Fluorescent Antibody Technique ; Follow-Up Studies ; Humans ; Immunoenzyme Techniques ; Male ; Middle Aged ; Neoplasm Recurrence, Local/genetics ; Neoplasm Staging ; Neuroendocrine Tumors/genetics ; Pancreatic Neoplasms/genetics ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Receptors, Somatostatin/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured
References:: Virchows Arch. 2006 Oct;449(4):395-401. (PMID: 16967267)
Cancer Res. 1988 Dec 15;48(24 Pt 1):6977-85. (PMID: 2903792)
PLoS One. 2014;9(1):e85527. (PMID: 24465589)
J Clin Oncol. 2008 Jun 20;26(18):3063-72. (PMID: 18565894)
N Engl J Med. 1996 Jan 25;334(4):246-54. (PMID: 8532003)
N Engl J Med. 2014 Jul 17;371(3):224-33. (PMID: 25014687)
Exp Eye Res. 2011 Feb;92(2):128-37. (PMID: 21147101)
Endocr Relat Cancer. 2011 Oct;18 Suppl 1:S17-25. (PMID: 22005113)
Front Neuroendocrinol. 2013 Aug;34(3):228-52. (PMID: 23872332)
Neuroendocrinology. 2010;91(3):268-78. (PMID: 20389030)
Trends Immunol. 2006 Dec;27(12):552-8. (PMID: 17045842)
J Clin Oncol. 2009 Oct 1;27(28):4656-63. (PMID: 19704057)
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11205-10. (PMID: 12163646)
FASEB J. 1999 Apr;13(6):647-55. (PMID: 10094925)
Eur J Clin Invest. 2007 Sep;37(9):700-8. (PMID: 17696959)
Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3480-9. (PMID: 17652715)
Oncotarget. 2015 Sep 29;6(29):27566-79. (PMID: 26259237)
Clin Cancer Res. 1997 Feb;3(2):265-72. (PMID: 9815682)
Am J Physiol Heart Circ Physiol. 2000 Jun;278(6):H1815-22. (PMID: 10843877)
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2640-5. (PMID: 18268320)
Onco Targets Ther. 2013 Apr 26;6:471-83. (PMID: 23667314)
Endocr Rev. 1997 Feb;18(1):4-25. (PMID: 9034784)
Eur J Endocrinol. 2007 Jan;156(1):65-74. (PMID: 17218727)
Oncogene. 2012 Apr 19;31(16):2049-61. (PMID: 21927030)
Mol Cell Endocrinol. 2008 May 14;286(1-2):40-8. (PMID: 17913342)
Int J Cancer. 2001 May 15;92(4):545-50. (PMID: 11304689)
Br J Cancer. 2013 Feb 5;108(2):429-37. (PMID: 23257898)
F1000 Med Rep. 2009 May 08;1:null. (PMID: 20948740)
Gastroenterology. 1991 Aug;101(2):303-11. (PMID: 1712329)
Exp Cell Res. 2006 Mar 10;312(5):630-41. (PMID: 16225862)
Theranostics. 2014;4(4):336-65. (PMID: 24578720)
Cell Mol Life Sci. 2010 Apr;67(7):1147-63. (PMID: 20063038)
Nat Rev Drug Discov. 2003 Dec;2(12):999-1017. (PMID: 14654798)
J Clin Endocrinol Metab. 2009 Jul;94(7):2634-43. (PMID: 19401364)
Mol Endocrinol. 2005 Jan;19(1):255-67. (PMID: 15388796)
Semin Oncol. 2013 Feb;40(1):56-68. (PMID: 23391113)
Eur J Cancer. 2001 May;37(8):1014-9. (PMID: 11334727)
Biochim Biophys Acta. 2003 Sep 22;1616(1):1-84. (PMID: 14507421)
Trends Cell Biol. 2005 Mar;15(3):138-45. (PMID: 15752977)
J Clin Endocrinol Metab. 2010 May;95(5):2497-502. (PMID: 20233783)
Endocrine. 2015 Nov;50(2):442-52. (PMID: 25854304)
Trends Endocrinol Metab. 2002 Dec;13(10):451-7. (PMID: 12431842)
Endocr Relat Cancer. 2010 Dec;17(4):897-908. (PMID: 20696814)
J Clin Endocrinol Metab. 2012 Mar;97(3):727-37. (PMID: 22170729)
Virchows Arch. 2007 Oct;451(4):757-62. (PMID: 17674042)
Oncologist. 2012;17(6):747-55. (PMID: 22628056)
Endocrinology. 2003 Apr;144(4):1574-84. (PMID: 12639942)
Cancer Res. 1990 Jun 15;50(12):3691-3. (PMID: 1971195)
Lancet Oncol. 2008 Jan;9(1):61-72. (PMID: 18177818)
J Pathol. 2003 Dec;201(4):515-27. (PMID: 14648654)
Contributed Indexing:: Keywords: angiogenesis; gastroenteropancreatic neuroendocrine tumors; neuroendocrine tumors; sst5TMD4; sst5TMD5
Substance Nomenclature:: 0 (Angiogenic Proteins)
0 (RNA, Messenger)
0 (Receptors, Somatostatin)
8X85ZJG6XJ (somatostatin receptor 5)
Entry Date(s):: Date Created: 20151218 Date Completed: 20161223 Latest Revision: 20181202
Update Code:: 20240104
PubMed Central ID:: PMC4872735
DOI:: 10.18632/oncotarget.6565
PMID:: 26673010
: Czasopismo naukowe

Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors, and their biological behavior is not well known. We studied the presence and potential functional roles of somatostatin receptors (sst1-5), focusing particularly on the truncated variants (sst5TMD4, sst5TMD5) and on their relationships with the angiogenic system (Ang/Tie-2 and VEGF) in human GEP-NETs.
Experimental Design: We evaluated 42 tumor tissue samples (26 primary/16 metastatic) from 26 patients with GEP-NETs, and 30 non-tumoral tissues (26 from adjacent non-tumor regions and 4 from normal controls) from a single center. Expression of sst1-5, sst5TMD4, sst5TMD5, Ang1-2, Tie-2 and VEGF was analyzed using real-time qPCR, immunofluorescence and immunohistochemistry. Expression levels were associated with tumor characteristics and clinical outcomes. Functional role of sst5TMD4 was analyzed in GEP-NET cell lines.
Results: sst1 exhibited the highest expression in GEP-NET, whilst sst2 was the most frequently observed sst-subtype (90.2%). Expression levels of sst1, sst2, sst3, sst5TMD4, and sst5TMD5 were significantly higher in tumor tissues compared to their adjacent non-tumoral tissue. Lymph-node metastases expressed higher levels of sst5TMD4 than in its corresponding primary tumor tissue. sst5TMD4 was also significantly higher in intestinal tumor tissues from patients with residual disease of intestinal origin compared to those with non-residual disease. Functional assays demonstrated that the presence of sst5TMD4 was associated to enhanced malignant features in GEP-NET cells. Angiogenic markers correlated positively with sst5TMD4, which was confirmed by immunohistochemical/fluorescence studies.
Conclusions: sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs.

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