Investigation of PACAP38 and PAC1 Receptor Expression in Human Retinoblastoma and the Effect of PACAP38 Administration on Human Y-79 Retinoblastoma Cells
Author:
Tóth Dénes1ORCID, Fábián Eszter2ORCID, Szabó Edina2, Patkó Evelin2, Vicena Viktória2, Váczy Alexandra2, Atlasz Tamás23ORCID, Tornóczky Tamás4, Reglődi Dóra2
Affiliation:
1. Department of Forensic Medicine, University of Pécs Medical School, Szigeti út 12, 7624 Pecs, Hungary 2. Department of Anatomy, HUN-REN-PTE PACAP Research Team, Centre for Neuroscience, University of Pécs Medical School, Szigeti út 12, 7624 Pecs, Hungary 3. Department of Sportbiology, University of Pécs, Ifjúság út 6, 7624 Pecs, Hungary 4. Department of Pathology, University of Pécs Medical School and Clinical Center, 7624 Pecs, Hungary
Abstract
Retinoblastoma represents the most prevalent malignant neoplasm affecting the eyes in childhood. The clear-cut origin of retinoblastoma has not yet been determined; however, based on experiments, it has been suggested that RB1 loss in cone photoreceptors causes retinoblastoma. Pituitary adenylate-cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide which has been shown to be affected in certain tumorous transformations, such as breast, lung, kidney, pancreatic, colon, and endocrine cancers. This study aimed to investigate potential changes in both PACAP38 and PAC1 receptor (PAC1R) expression in human retinoblastoma and the effect of PACAP38 administration on the survival of a human retinoblastoma cell line (Y-79). We analyzed human enucleation specimens removed because of retinoblastoma for PACAP38 and PAC1R immunostaining and the effect of PACAP38 on the survival of the Y-79 cell line. We described for the first time that human retinoblastoma cells from patients showed only perinuclear, dot-like immunopositivity for both PACAP38 and PAC1R, irrespective of laterality, genetic background, or histopathological features. Nanomolar (100 nM and 500 nM) PACAP38 concentrations had no effect on the viability of Y-79 cells, while micromolar (2 µM and 6 µM) PACAP38 significantly decreased tumor cell viability. These findings, along with general observations from animal studies showing that PACAP38 has strong anti-apoptotic, anti-inflammatory, and antioxidant effects on ocular tissues, together suggest that PACAP38 and its analogs are promising candidates in retinoblastoma therapy.
Funder
Hungarian Brain Research Program Thematic Excellence Program 2021 Hungarian Scientific Research Fund
Subject
Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics
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