PACAP and PAC1 Receptor Expression in Human Insulinomas

Sandor Ferencz,Balint Kaszas,Viktoria Vicena,Dora Reglodi,Oszkar Karadi,Dezso Kelemen,Sebastian Bardosi,Denes Toth

doi:10.1007/s10989-021-10204-0

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with widespread occurrence and diverse functions. PACAP binds to specific PAC1 and non-specific VPAC1/2 receptors. PACAP is considered as a growth factor, as it plays important roles during development and participates in reparative processes. Highest concentrations are found in the nervous system and endocrine glands, where several functions are known, including actions in tissue growth, differentiation and tumour development. Therefore, we have investigated expression of PACAP and its receptors in different tumours, including those of endocrine glands. We showed earlier that PACAP and PAC1 receptor staining intensity decreased in pancreatic ductal adenocarcinoma. In the present study we aimed to investigate alterations of PACAP and PAC1 receptor in human insulinoma and compared the immunostaining pattern with samples from chronic pancreatitis patients. We collected perioperative and histological data of patients who underwent operation because of insulinoma or chronic pancreatitis over a five-year-long period. Histology showed chronic pancreatitis with severe scar formation in pancreatitis patients, while tumour samples evidenced Grade 1 or 2 insulinoma. PACAP and PAC1 receptor expression was studied using immunohistochemistry. Staining intensity was very strong in the Langerhans islets of normal tissue and discernible staining was also observed in the exocrine pancreas. Immunostaining intensity for both PACAP and PAC1 receptor was markedly weaker in insulinoma samples, and disappeared from chronic pancreatitis samples except for intact islets. These findings show that PAC1 receptor/PACAP signalling is altered in insulinoma and this suggests a possible involvement of this system in tumour growth or differentiation.

Highlights

Both benign and malignant pancreas diseases are frequent
We found a decreased or diminished peptide and receptor expression in the insulinoma parts compared to the normal tissue
This finding is similar to our earlier observation in pancreatic ductal adenocarcinoma, where we found diminished expression of Pituitary adenylate cyclase activating polypeptide (PACAP) and PAC1 receptor in the adenocarcinoma parts compared to normal exocrine acini

Summary

Introduction

Both benign and malignant pancreas diseases are frequent. Adenocarcinoma of the pancreas is among the most malignant tumours, while acute and chronic pancreatitis affect a large population all around the world. Chronic pancreatitis is associated with repeated inflammations, causing tissue fibrosis, often pain and destruction of the pancreas. It affects both the endocrine and the exocrine parts of the organ, with need for specific nutrition and diet (Gress et al 1994a, b; Michalski et al 2008; Wiese et al 2020). Some symptoms of chronic pancreatitis and pancreas carcinoma are similar and because of the non-specific symptoms correct diagnosis and definite decision is difficult to make. Based on these facts, severe chronic pancreatitis and suspect tumour onset represent operative indication

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