PMID- 26259237
OWN - NLM
STAT- MEDLINE
DCOM- 20160816
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 29
DP  - 2015 Sep 29
TI  - Inverse expression of somatostatin and CXCR4 chemokine receptors in 
      gastroenteropancreatic neuroendocrine neoplasms of different malignancy.
PG  - 27566-79
LID - 10.18632/oncotarget.4491 [doi]
AB  - INTRODUCTION: Somatostatin receptors (SSTR) are widely distributed in 
      well-differentiated neuroendocrine neoplasms (NEN) and serve as primary targets 
      for diagnostics and treatment. An overexpression of the chemokine receptor CXCR4, 
      in contrast, is considered to be present mainly in highly proliferative and 
      advanced tumors. Comparative data are still lacking, however, for neuroendocrine 
      carcinomas (NEC). METHODS: SSTR subtype (1, 2A, 3, 5) and CXCR4 expression was 
      evaluated in G1 (n = 31), G2 (n = 47), and low (G3a; Ki-67: 21-49%; n = 21) and 
      highly proliferative (G3b; Ki-67: >50%, n = 22) G3 (total n = 43) 
      gastroenteropancreatic NEN samples by performing immunohistochemistry with 
      monoclonal rabbit anti-human anti-SSTR and anti-CXCR4 antibodies, respectively, 
      and was correlated with clinical data. RESULTS: Both CXCR4 and SSTR were widely 
      expressed in all tumors investigated. CXCR4 expression differed significantly 
      between the G1 and G3 specimens and within the G3 group (G3a to G3b), and was 
      positively correlated with Ki-67 expression. SSTR2A, in contrast, exhibited an 
      inverse association with Ki-67. SSTR2A was highly expressed in G1 and G2 tumors, 
      but was significantly less abundant in G3 carcinomas. Additionally, SSTR1 
      expression was higher in G3a than in G3b tumors. CONCLUSION: We observed an 
      elevation in CXCR4 and a decrease in SSTR2A expression with increasing 
      malignancy. Interestingly, 23% of the G3 specimens had strong SSTR2A expression. 
      Because CXCR4 was strongly expressed in highly proliferative G3 carcinomas, it is 
      an interesting new target and needs to be validated in larger studies.
FAU - Kaemmerer, Daniel
AU  - Kaemmerer D
AD  - Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, 
      Germany.
FAU - Trager, Tina
AU  - Trager T
AD  - Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, 
      Germany.
AD  - Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich 
      Schiller University, Jena, Germany.
FAU - Hoffmeister, Maike
AU  - Hoffmeister M
AD  - Institute of Pathology, University Hospital Tuebingen, Germany.
FAU - Sipos, Bence
AU  - Sipos B
AD  - Institute of Pathology, University Hospital Tuebingen, Germany.
FAU - Hommann, Merten
AU  - Hommann M
AD  - Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, 
      Germany.
FAU - Sanger, Jorg
AU  - Sanger J
AD  - Institute of Pathology and Cytology, Bad Berka, Germany.
FAU - Schulz, Stefan
AU  - Schulz S
AD  - Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich 
      Schiller University, Jena, Germany.
FAU - Lupp, Amelie
AU  - Lupp A
AD  - Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich 
      Schiller University, Jena, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Receptors, Somatostatin)
RN  - 51110-01-1 (Somatostatin)
RN  - D73QL0OMU2 (somatostatin receptor 2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cell Proliferation
MH  - Female
MH  - Gastrointestinal Neoplasms/*metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Ki-67 Antigen/metabolism
MH  - Liver Neoplasms/metabolism/secondary
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neuroendocrine Tumors/*metabolism
MH  - Pancreatic Neoplasms/*metabolism
MH  - Receptors, CXCR4/*metabolism
MH  - Receptors, Somatostatin/*metabolism
MH  - Somatostatin/*metabolism
MH  - Treatment Outcome
PMC - PMC4695009
OTO - NOTNLM
OT  - CXCR4
OT  - chemokine receptor
OT  - neuroendocrine carcinoma
OT  - neuroendocrine tumor
OT  - somatostatin receptor
COIS- CONFLICTS OF INTEREST Kaemmerer D. received support for travelling to meetings by 
      the companies IPSEN and PFIZER. All other authors declare no conflict of 
      interests.
EDAT- 2015/08/11 06:00
MHDA- 2016/08/17 06:00
PMCR- 2015/09/29
CRDT- 2015/08/11 06:00
PHST- 2015/04/13 00:00 [received]
PHST- 2015/07/03 00:00 [accepted]
PHST- 2015/08/11 06:00 [entrez]
PHST- 2015/08/11 06:00 [pubmed]
PHST- 2016/08/17 06:00 [medline]
PHST- 2015/09/29 00:00 [pmc-release]
AID - 4491 [pii]
AID - 10.18632/oncotarget.4491 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Sep 29;6(29):27566-79. doi: 10.18632/oncotarget.4491.