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Neurotensin receptors in pancreatic ductal carcinomas
Meike Körner1, Beatrice Waser1, Oliver Strobel2
1Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, PO Box 62, Murtenstrasse 31, CH-3010 Berne, Switzerland.
Background:
The frequent expression of neurotensin receptors (NT-R) in primaries of pancreatic ductal carcinomas has triggered the development of radioactive neurotensin analogs for possible in vivo targeting of these tumors. However, the complete lack of information regarding NT-R in liver metastases of pancreatic cancer and pancreatic intraepithelial neoplasia (PanIN) makes an in vitro study of NT-R in these tissues indispensable.
Methods:
Using in vitro receptor autoradiography with (125)I-[Tyr(3)]-neurotensin, NT-R were investigated in 18 primaries and 23 liver metastases of pancreatic ductal carcinomas as well as in 19 PanIN lesions.
Results:
We report here that 13 of 18 ductal carcinoma primaries and 14 of 23 liver metastases expressed NT-R. Moreover, none of the six PanIN 1B cases expressed NT-R, while two of six PanIN 2 and five of seven PanIN 3 expressed NT-R. Binding was fully displaced by the type 1 NT-R-selective antagonist SR48692, indicating that the NT-R in the tumors are of the type 1 NT-R subtype.
Conclusions:
These in vitro data extend the currently available information on NT-R in invasive and non-invasive pancreatic ductal tumors. They suggest that type 1 NT-R may be a novel, specific marker of PanIN of higher degree. The high expression of NT-R in primaries and metastases of invasive cancer strongly support the need to develop radioactive neurotensin analogs for the diagnosis and therapy of this tumor type.
Insights
Neurotensin receptors (NT-R) are present in pancreatic cancer metastases and higher-grade PanIN lesions. This suggests NT-R as a potential diagnostic and therapeutic target for pancreatic cancer.
Area of Science:
- Oncology
- Molecular Imaging
- Receptor Biology
Background:
- Neurotensin receptors (NT-R) are frequently found in primary pancreatic ductal carcinomas.
- Targeting these receptors with radioactive neurotensin analogs is a potential therapeutic strategy.
- NT-R expression in pancreatic cancer liver metastases and PanIN remains largely uncharacterized.
Purpose of the Study:
- To investigate NT-R expression in pancreatic ductal carcinoma primaries, liver metastases, and PanIN lesions.
- To determine the subtype of NT-R present in these pancreatic tissues.
- To assess the potential of NT-R as a biomarker for pancreatic cancer progression.
Main Methods:
- In vitro receptor autoradiography was employed.
- (125)I-[Tyr(3)]-neurotensin was used to detect NT-R.
- Analysis included 18 primary tumors, 23 liver metastases, and 19 PanIN lesions.
Main Results:
- NT-R were detected in 13/18 primary tumors and 14/23 liver metastases.
- NT-R expression was absent in PanIN 1B but present in 2/6 PanIN 2 and 5/7 PanIN 3 lesions.
- Antagonist SR48692 confirmed the presence of type 1 NT-R in all positive samples.
Conclusions:
- This study provides in vitro data on NT-R in invasive and non-invasive pancreatic tumors.
- Type 1 NT-R may serve as a specific marker for higher-grade PanIN.
- High NT-R expression in primary and metastatic pancreatic cancer supports developing radiolabeled neurotensin analogs for diagnosis and therapy.
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