Current concepts in neuroendocrine cancer metabolism

Abstract

Neuroendocrine (NE) cancers occur in multiple anatomic locations and range in prognosis from indolent to aggressive. In addition, adenocarcinomas can express gene products associated with NE cells, referred to as NE differentiation (NED), which correlates with poor prognosis and aggressive disease. Several metabolites and peptides produced by NE cells have been discovered that engage in cellular signaling and have autocrine and paracrine effects on cancer cell proliferation. This review focuses on the current knowledge of small molecule metabolism in NE cancers involving the synthesis of biogenic amine, polyamine, and amino acid neurotransmitters. Systems biology-directed approaches to NE cancer metabolism using gene expression profiling, liquid chromatography/mass spectrometry (LC/MS) and nuclear magnetic resonance (NMR) are also discussed. Furthermore, knowledge of metabolic and signaling pathways in NE cancers has led to the successful implementation of therapeutic regimens in cell culture and animal models of NE carcinogenesis.

A side-by-side evaluation of [18F]FDOPA enantiomers for non-invasive detection of neuroendocrine tumors by positron emission tomography

“…However, interestingly and contrary to the trends observed for [ 18 F]FDOPA, D-[ 18 F]FDOPA showed higher non-specific retention in STC-1 mice over 120min post tracer administration. Although, biodistribution of [ 18 F]FDOPA enantiomers were not previously addressed until this report, our findings are still in line with published studies showing variable amino acid requirements among NET subtypes [37]. For instance, pheochromocytomas process/metabolize higher levels of amino acids, compared to other NETs, leading to elevated secretion of the catecholamines, metanephrine and normetanephrine, to such an extent that plasma metanephrine levels are currently used as a sensitive diagnostic indicator for this malignancy [38].…”

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“…However, interestingly and contrary to the trends observed for [ 18 F]FDOPA, D-[ 18 F]FDOPA showed higher nonspecific retention in STC-1 mice over 120min post tracer administration. Although, biodistribution of [ 18 F]FDOPA enantiomers were not previously addressed until this report, our findings are still in line with published studies showing variable amino acid requirements among NET subtypes [37]. For instance, pheochromocytomas process/ metabolize higher levels of amino acids, compared to other NETs, leading to elevated secretion of the catecholamines, metanephrine and normetanephrine, to such an extent that plasma metanephrine levels are currently used as a sensitive diagnostic indicator for this malignancy [38].…”

Ectopic Hypothalamic and Pituitary Hormone Secreting Syndromes

“…These cells, normally associated with peptide production, are multipotential and migratory in nature; (3) the neuroendocrine (NE) system was originally described by Pearse 5 as a diffuse collection of secretory cells possessing the properties of amine precursor uptake and decarboxylase (APUD). 7 Proof of ectopic hormone production is validated by certain criteria. In additional, these cells were found to synthesize polypeptide hormones.…”

“…These cells may display hyperplasia and secrete at least 1 amine and/or polypeptide in excessive amounts. 7,10 In contrast, adenocarcinomas can also exhibit NE features by means of NE differentiation, characterized by the expression of the gene products of NE cells. 9 Neoplasms that arise from NE cells occur virtually in all anatomic locations and display a wide range of aggressiveness ranging from benign to metastatic tumors.…”