PACAP and PAC1 Receptor Expression in Human Insulinomas

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.

Pituitary Adenylate Cyclase Activating Polypeptide Has Inhibitory Effects on Melanoma Cell Proliferation and Migration In Vitro

“…In certain neural cells PACAP is able to enhance, while in other cells it can decrease the rate of cell divisions (57). Specifically in neoplastic cells, extrinsic PACAP has been shown to have opposing effects on proliferation of breast cancer cells (28,58). In our experiments, we observed reduced proliferation of melanoma cells upon PACAP 1-38 treatments but slight elevation was shown in the presence of the antagonist.…”

“…Contradictory PACAP effects have been reported in the field of oncology (28). Functions of PACAP are controversial in different tumours as it can inhibit the migration of certain tumour cells such as glioblastoma cells (29) or reduce the tumour growth in cervical cancer (30).…”

“…Although the effects of PACAP have been identified in sweat glands (36), and in keratinocytes (37,38), no data can be found on melanocytes. Moreover, the presence of PACAP receptors has been studied in different tumours such as colon, ovarian, breast, lung, prostate, liver or pancreatic cancers (28,34), but no information can be found related to melanoma. Therefore, the goal of our present study is to examine the presence of PACAP receptors in melanocytes and melanoma cells in vivo and in vitro.…”