RT Journal Article
T1 Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors.
A1 Sampedro-Nuñez, Miguel
A1 Luque, Raul M
A1 Ramos-Levi, Ana M
A1 Gahete, Manuel D
A1 Serrano-Somavilla, Ana
A1 Villa-Osaba, Alicia
A1 Adrados, Magdalena
A1 Ibañez-Costa, Alejandro
A1 Martin-Perez, Elena
A1 Culler, Michael D
A1 Marazuela, Monica
A1 Castaño, Justo P
K1 Angiogenesis
K1 Gastroenteropancreatic neuroendocrine tumors
K1 Neuroendocrine tumors
K1 sst5TMD4
K1 sst5TMD5
AB 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. 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. 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. sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs.
PB Impact Journals LLC
YR 2015
FD 2015-11-21
LK http://hdl.handle.net/10668/9666
UL http://hdl.handle.net/10668/9666
LA en
NO Sampedro-Núñez M, Luque RM, Ramos-Levi AM, Gahete MD, Serrano-Somavilla A, Villa-Osaba A, et al. Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors. Oncotarget. 2016 Feb 9;7(6):6593-608
DS RISalud
RD Apr 6, 2025