Neuropeptide Y receptor expression in human primary ovarian neoplasms

Abstract

Peptide hormone receptors overexpressed in human malignant neoplasms are potential targets for diagnostic scintigraphy and radiotherapy. One such receptor is the neuropeptide Y (NPY) receptor, mediating primarily feeding behavior in the brain but shown recently to play a role in breast cancer. In this study, the presence of NPY receptors was evaluated in another group of gynecological tumors, namely ovarian tumors, using in vitro receptor autoradiography with 125 I-labeled peptide YY and receptor subtype selective analogs. Remarkably, all 10 investigated inhibin-expressing granulosa cell tumors, Leydig cell tumors, and Sertoli-Leydig cell tumors expressed NPY receptors. In contrast, receptors were found in only seven of 22 ovarian adenocarcinomas (32%). Pharmacological characterization of the expressed NPY receptor subtypes in the various tumors revealed the presence of Y1, Y2, or both. In addition, Y1 receptors were observed in intra-and peritumoral blood vessels as well. NPY receptors were not expressed in three ovarian adenomas, three borderline tumors, four fibromas and fibrothecomas, and one dysgerminoma. This is the first time that NPY receptors are described in human ovarian tissue. They may play a role in the pathogenesis and also in the pathophysiology of ovarian malignancies. Moreover, the high incidence and density of NPY receptors in sex cord-stromal tumors suggest that these receptors represent a new potential target for the diagnostic and therapeutic administration of NPY analogs in these tumors.

Global differential gene expression in the pituitary gland and the ovaries of pre- and postpubertal Brahman heifers

“…In particular, when a high concentration of estrogen level is present, NPY stimulates the secretion of GnRH, and when estrogen levels are low, NPY inhibits GnRH release (Celik et al, 2015). Although NPY is mostly expressed in the mammalian brain, it is also expressed in human primary ovarian neoplasms (Körner et al, 2003), in rat ovaries (McDonald et al, 1987), and in bovine ovaries (Hulshof et al, 1994) as well as ovine ovaries (Keator et al, 2010). Our study showed differential expression of NPY and NPY2R in ovaries when preand postpubertal heifers were compared.…”

Relevance of the Neuropeptide Y System in the Biology of Cancer Progression

“…(1); the Y4-R preferring ligand human PP; and the Y5-R selective [Ala 31 , Aib 32 ]-hNPY) ruled out the presence of Y4-R and Y5-R subtypes, whereas confirmed that of Y1-R and Y2-R. However, they were present only in 32% of a series of ovarian adenocarcinomas, and were not necessarily present in the same areas [81].…”

Red-fluorescent argininamide-type NPY Y1 receptor antagonists as pharmacological tools

“…The synthesis of commercially unavailable linkers is shown in Scheme 2. Glutaric acid derivatives 16 31 and 17 were obtained through treatment of mono Boc-protected ethane-1,2-diamine (14) and propane-1,3-diamine (15), respectively. The N-Cbz protected x-amino carboxylic acid 19 was prepared from the tert-butyl ester of x-amino carboxylic acid 18 via preparation of the benzylcarbamate (Cbz-protection) followed by cleavage of the tert-butyl ester.…”

“…The Y 1 R was selected as a representative model of a peptidergic GPCR, for instance, as this receptor subtype was recently associated with diagnosis and treatment of tumours. [11][12][13][14][15][16][17][18][19] For the synthesis of non-peptidic fluorescent ligands, the argininamidetype Y 1 R selective antagonists BIBP 3226 20 and BIBO 3304 21 ( Fig. 1) were considered appropriate parent molecules to construct high affinity fluorescent probes with reduced propensity to induce internalisation compared to (peptidic) agonists.…”