Intricacies of the Molecular Machinery of Catecholamine Biosynthesis and Secretion by Chromaffin Cells of the Normal Adrenal Medulla and in Pheochromocytoma and Paraganglioma.
PPGL
adrenomedullary function
catecholamines
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
06 Aug 2019
06 Aug 2019
Historique:
received:
22
06
2019
revised:
11
07
2019
accepted:
12
07
2019
entrez:
9
8
2019
pubmed:
9
8
2019
medline:
9
8
2019
Statut:
epublish
Résumé
The adrenal medulla is composed predominantly of chromaffin cells producing and secreting the catecholamines dopamine, norepinephrine, and epinephrine. Catecholamine biosynthesis and secretion is a complex and tightly controlled physiologic process. The pathways involved have been extensively studied, and various elements of the underlying molecular machinery have been identified. In this review, we provide a detailed description of the route from stimulus to secretion of catecholamines by the normal adrenal chromaffin cell compared to chromaffin tumor cells in pheochromocytomas. Pheochromocytomas are adrenomedullary tumors that are characterized by uncontrolled synthesis and secretion of catecholamines. This uncontrolled secretion can be partly explained by perturbations of the molecular catecholamine secretory machinery in pheochromocytoma cells. Chromaffin cell tumors also include sympathetic paragangliomas originating in sympathetic ganglia. Pheochromocytomas and paragangliomas are usually locally confined tumors, but about 15% do metastasize to distant locations. Histopathological examination currently poorly predicts future biologic behavior, thus long term postoperative follow-up is required. Therefore, there is an unmet need for prognostic biomarkers. Clearer understanding of the cellular mechanisms involved in the secretory characteristics of pheochromocytomas and sympathetic paragangliomas may offer one approach for the discovery of novel prognostic biomarkers for improved therapeutic targeting and monitoring of treatment or disease progression.
Identifiants
pubmed: 31390824
pii: cancers11081121
doi: 10.3390/cancers11081121
pmc: PMC6721535
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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