PACAP and PAC1 receptor expression in pancreatic ductal carcinoma

Ferencz, A.; Reglődi, Dóra; Kaszás, Bálint; Bardosi, A.; Tóth, Dénes; Vekony, Zsofia; Vicena, Viktoria; Karádi, O.; Kelemen, Dezső

doi:10.3892/ol.2019.10971

Cited by 8 publications

(14 citation statements)

References 62 publications

(57 reference statements)

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“…PACAP has also been described in the exocrine pancreas, which is analogous to a serous salivary gland in structure (Schmidt et al 1993). The endocrine part of the pancreas, containing the islets of Langerhans, expresses markedly high levels of PACAP, similarly to other endocrine glands (Ferencz et al 2019). The intrapancreatic PACAP has an important effect in the regulation of beta cell proliferation (Sakurai et al 2011) and it plays an important regulatory role in both insulin and glucagon secretion.…”

Section: Introductionmentioning

confidence: 99%

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PACAP and PAC1 Receptor Expression in Human Insulinomas

Ferencz

Tóth

Kaszás

et al. 2021

Int J Pept Res Ther

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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.

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Section: Introductionmentioning

confidence: 99%

“…In the carcinoma samples there was no PACAP immunostaining. We supposed that the lack of PAC1 receptor/PACAP signalling could have an impact on growth and differentiation of pancreas adenocarcinoma (Ferencz et al 2019). However, it is not known how expression of PACAP and its specific receptor change in pancreas insulinoma.…”

Section: Introductionmentioning

confidence: 99%

PACAP and PAC1 Receptor Expression in Human Insulinomas

Ferencz

Tóth

Kaszás

et al. 2021

Int J Pept Res Ther

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“…Occurrence of PACAP and receptors has been shown in several exocrine glands and their secretions, including salivary, mammary and lacrimal gland (85,114,(118)(119)(120)(121). Among others, PACAP enhances salivary and lacrimal gland secretion, increases salivary gland blood flow, and is implicated in breast cancer growth (85,118,(122)(123)(124)(125).…”

Section: Salivary and Other Exocrine Glandsmentioning

confidence: 99%

“…PACAP is present in both the exocrine pancreas and in the endocrine islets of Langerhans and it is thought to be a potent intra-pancreatic regulator of beta cells under physiological and pathological conditions ( 112 – 114 ). Interestingly, cerulein-induced pancreatitits was aggravated in PACAP deficient mice ( 64 ), but pancreatic beta cells derived from rat insulinoma, key elements in pathogenesis in diabetes mellitus, were prevented from streptozotocin-induced cell death ( 18 ).…”

Section: Digestive Systemmentioning

confidence: 99%

Protective Effects of PACAP in Peripheral Organs

et al. 2020

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide widely distributed in the nervous system, where it exerts strong neuroprotective effects. PACAP is also expressed in peripheral organs but its peripheral protective effects have not been summarized so far. Therefore, the aim of the present paper is to review the existing literature regarding the cytoprotective effects of PACAP in non-neuronal cell types, peripheral tissues, and organs. Among others, PACAP has widespread expression in the digestive system, where it shows protective effects in various intestinal pathologies, such as duodenal ulcer, small bowel ischemia, and intestinal inflammation. PACAP is present in both the exocrine and endocrine pancreas as well as liver where it reduces inflammation and steatosis by interfering with hepatic pathology related to obesity. It is found in several exocrine glands and also in urinary organs, where, with its protective effects being mainly published regarding renal pathologies, PACAP is protective in numerous conditions. PACAP displays anti-inflammatory effects in upper and lower airways of the respiratory system. In the skin, it is involved in the development of inflammatory pathology such as psoriasis and also has anti-allergic effects in a model of contact dermatitis. In the non-neuronal part of the visual system, PACAP showed protective effects in pathological conditions of the cornea and retinal pigment epithelial cells. The positive role of PACAP has been demonstrated on the formation and healing processes of cartilage and bone where it also prevents osteoarthritis and rheumatoid arthritis development. The protective role of PACAP was also demonstrated in the cardiovascular system in different pathological processes including hyperglycaemia-induced endothelial dysfunction and age-related vascular changes. In the heart, PACAP protects against ischemia, oxidative stress, and cardiomyopathies. PACAP is also involved in the protection against the development of pre-senile systemic amyloidosis, which is presented in various peripheral organs in PACAP-deficient mice. The studies summarized here provide strong evidence for the cytoprotective effects of the peptide. The survival-promoting effects of PACAP depend on a number of factors which are also shortly discussed in the present review.

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“…Among tissues, PACAP occurs at highest concentrations in the brain and endocrine glands [8], but numerous peripheral tissues also have detectable levels. Altered PACAP expression in human tissues was demonstrated in several pathological conditions, like ductal adenocarcinoma of the pancreas [35], papillary carcinoma of the thyroid gland [36], ischemic heart disease [37] and inflammatory bowel disease [38]. In the brain, PACAP expression could be examined from postmortem human samples, where a manifest reduction was observed in Alzheimer's disease, in the temporal, frontal and occipital lobes [39,40].…”

Section: General Overviewmentioning

confidence: 99%

The Neuroprotective and Biomarker Potential of PACAP in Human Traumatic Brain Injury

Tóth

Tamás

Reglődi

2020

IJMS

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Traumatic brain injury remains a growing public health concern and represents the greatest contributor to death and disability globally among all trauma-related injuries. There are limited clinical data regarding biomarkers in the diagnosis and outcome prediction of TBI. The lack of real effective treatment for recovery calls for research of TBI to be shifted into the area of prevention, treatment of secondary brain injury and neurorehabilitation. The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has been reported to act as a hormone, a neuromodulator, a neurotransmitter and a trophic factor, and has been implicated in a variety of developmental and regenerative processes. The importance of PACAP in neuronal regeneration lies in the upregulation of endogenous PACAP and its receptors and the protective effect of exogenous PACAP after different central nervous system injury. The aim of this minireview is to summarize both the therapeutic and biomarker potential of the neuropeptide PACAP, as a novel possible target molecule presently being investigated in several human conditions including TBI, and with encouraging results in animal models of TBI.

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PACAP and PAC1 receptor expression in pancreatic ductal carcinoma

Cited by 8 publications

References 62 publications

PACAP and PAC1 Receptor Expression in Human Insulinomas

PACAP and PAC1 Receptor Expression in Human Insulinomas

Protective Effects of PACAP in Peripheral Organs

The Neuroprotective and Biomarker Potential of PACAP in Human Traumatic Brain Injury

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