Expression of PACAP and PAC1 Receptor in Normal Human Thyroid Gland and in Thyroid Papillary Carcinoma

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor. PACAP and PAC1 receptor expressions were investigated from thyroid gland samples of patients with papillary carcinomas. The staining intensity of follicular epithelial cells and thyroid colloid of tumor tissue was compared to that of tumor-free tissue in the same thyroid glands in a semi-quantitative way. Our results reveal that both PACAP(-like) and PAC1 receptor(-like) immunoreactivities are altered in papillary carcinoma. Stronger PACAP immunoreactivity was observed in active follicles. Colloidal PACAP immunostaining was either lacking or very weak, and more tumorous cells displayed strong apical immunoreactivity. Regarding PAC1 receptor, cells of the normal thyroid tissue showed strong granular expression, which was lacking in the tumor cells. The cytoplasm of tumor cells displayed weak, minimal staining, while in a few tumor cells we observed strong PAC1 receptor expression. This pattern was similar to that observed in the PACAP expression, but fewer in number. In summary, we showed alteration of PACAP and PAC1 receptor expression in human thyroid papillary carcinoma, indicating that PACAP regulation is disturbed in tumorous tissue of the thyroid gland. The exact role of PACAP in thyroid tumor growth should be further explored.

PACAP and PAC1 receptor expression in pancreatic ductal carcinoma

“…Sections were stained using standard immunohistochemistry with human anti-PACAP antibody (dilution of 1:200; Peninsula, CA, USA) and with human PAC1 receptor antibody raised in rabbit (dilution of 1:200; Sigma-Aldrich, Budapest, Hungary). Immunohistochemical staining was performed with EnVision FLEX Visualization Systems for Dako Omins (Dako, Denmark), similarly to our earlier descriptions (37). Liquid fast-red substrate kit (Abcam, UK) was used as a chromogen for the immunohistochemical staining.…”

“…Stimulative role of tumour genesis of PACAP is proven by stimulation of c-Fos as well as c-Jun transcription, and PACAP strongly induces proliferation of the rat pancreatic carcinoma cell line AR4-2J via interaction with the G-protein coupled type 1 PACAP/VIP (PV1) receptor (36). PACAP and PAC1 receptor display specific alterations in several different tumour types, such as thyroid papillary carcinoma and testicular cancer (37,38). It is not known how expression of the peptide and its specific receptor changes in pancreatic cancer.…”

Retinoprotective Effects of TAT-Bound Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Polypeptide

“…PACAP has a widespread occurrence in the body and a broad array of functions (Reglodi and Tamas 2016 ). Among others, PACAP influences gastrointestinal, urinary and cardiovascular functions (Heppner et al 2018 ; Parsons and May 2018 ; Reglodi et al 2018a ), plays a role in reproduction and pregnancy (Lajko et al 2018 ; Reglodi et al 2012 ; Ross et al 2018 ), has diverse behavioral and cognitive functions (Farkas et al 2017 ; Gupta et al 2018 ; Han et al 2014 ; King et al 2017 ), plays roles during both early development and aging (Fulop et al 2018 ; Reglodi et al 2018b ; Watanabe et al 2007 ), as well as influences the functions of both endocrine and exocrine glands (Bardosi et al 2016 ; Egri et al 2016 ; Prevost et al 2013 ; Sasaki et al 2017 ). VIP has also been shown to have diverse actions in addition to the originally described vasodilatory effects (Gozes 2008 ; Hill et al 2007 ; Moody and Gozes 2007 ; Vu et al 2015 ).…”

Passage through the Ocular Barriers and Beneficial Effects in Retinal Ischemia of Topical Application of PACAP1-38 in Rodents

“…PACAP exists in two biologically active forms, PACAP1-27 and PACAP1-38. PACAP has a wide variety of diverse biological effects in different cells and tissues, from thermoregulatory effects [1], actions on cardiac excitability [2], thyroid gland functions [3], chondrogenesis [4] and muscle contraction [5]. Among the well-established and most intensively studied actions are PACAP’s neurotrophic and neuroprotective effects.…”