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Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin

SIMPLE SUMMARY: Insulin-regulated aminopeptidase (IRAP) is a well-known enzyme involved mainly in the regulation of the peptide hormones, oxytocin and vasopressin. However, this enzyme activity has hardly been analyzed in breast cancer patients. Additionally, the influence of both the hormonal statu...

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Autores principales: Ramírez-Expósito, María Jesús, Dueñas-Rodríguez, Basilio, Carrera-González, María Pilar, Navarro-Cecilia, Joaquín, Martínez-Martos, Jose Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694176/
https://www.ncbi.nlm.nih.gov/pubmed/33158090
http://dx.doi.org/10.3390/cancers12113252
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author Ramírez-Expósito, María Jesús
Dueñas-Rodríguez, Basilio
Carrera-González, María Pilar
Navarro-Cecilia, Joaquín
Martínez-Martos, Jose Manuel
author_facet Ramírez-Expósito, María Jesús
Dueñas-Rodríguez, Basilio
Carrera-González, María Pilar
Navarro-Cecilia, Joaquín
Martínez-Martos, Jose Manuel
author_sort Ramírez-Expósito, María Jesús
collection PubMed
description SIMPLE SUMMARY: Insulin-regulated aminopeptidase (IRAP) is a well-known enzyme involved mainly in the regulation of the peptide hormones, oxytocin and vasopressin. However, this enzyme activity has hardly been analyzed in breast cancer patients. Additionally, the influence of both the hormonal status (pre or postmenopause) and the administration of neoadjuvant chemotherapy have rarely been studied. We show that there is a weak association between IRAP activity and the circulating levels of peptide hormones with variations depending on the hormonal status and the neoadjuvant treatment, and propose a role beyond oxytocin and vasopressin regulation that is related to the local mammary renin-angiotensin system and glucose transportation to the cells. ABSTRACT: Insulin-regulated aminopeptidase (IRAP) is the only enzyme known to cleave oxytocin and vasopressin; however, it is also the high-affinity binding site for angiotensin IV (AngIV) receptor type 4 (AT4) ligands and it is related to insulin-dependent glucose transporters through the translocation of the glucose transporter type 4 (GLUT4). Previous studies have demonstrated an association between IRAP activity and the number and size of mammary tumors in an animal model of breast cancer (BC). Also, a highly significant increase in IRAP activity has been found in BC tissue from women patients. Here, we found no changes in circulating IRAP in premenopausal (preMP) women, but it increased significantly in postmenopausal (postMP) women not treated with neoadjuvant chemotherapy (NACH). However, in women treated with NACH, IRAP activity increased in both preMP and postMP women. Two years of follow-up indicated lower levels of IRAP activity in untreated preMP women, but a return to control levels in untreated postMP women, while IRAP activity returned to control levels in women treated with NACH. Circulating oxytocin decreased in both preMP and postMP women during the follow-up period. Differences in Oxytocin appeared between preMP and postMP women treated with NACH, but not in women who were not treated with NACH. On the contrary, circulating vasopressin increased in untreated and treated preMP and postMP women, with most of the differences related to the hormonal status as well as the neoadjuvant treatment during the two year follow-up We propose that IRAP is involved in mechanisms related not only to oxytocin and/or vasopressin regulation, but also to the local mammary RAS through AngIV and its role in glucose transportation through the IRAP/GLUT4 system.
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spelling pubmed-76941762020-11-28 Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin Ramírez-Expósito, María Jesús Dueñas-Rodríguez, Basilio Carrera-González, María Pilar Navarro-Cecilia, Joaquín Martínez-Martos, Jose Manuel Cancers (Basel) Article SIMPLE SUMMARY: Insulin-regulated aminopeptidase (IRAP) is a well-known enzyme involved mainly in the regulation of the peptide hormones, oxytocin and vasopressin. However, this enzyme activity has hardly been analyzed in breast cancer patients. Additionally, the influence of both the hormonal status (pre or postmenopause) and the administration of neoadjuvant chemotherapy have rarely been studied. We show that there is a weak association between IRAP activity and the circulating levels of peptide hormones with variations depending on the hormonal status and the neoadjuvant treatment, and propose a role beyond oxytocin and vasopressin regulation that is related to the local mammary renin-angiotensin system and glucose transportation to the cells. ABSTRACT: Insulin-regulated aminopeptidase (IRAP) is the only enzyme known to cleave oxytocin and vasopressin; however, it is also the high-affinity binding site for angiotensin IV (AngIV) receptor type 4 (AT4) ligands and it is related to insulin-dependent glucose transporters through the translocation of the glucose transporter type 4 (GLUT4). Previous studies have demonstrated an association between IRAP activity and the number and size of mammary tumors in an animal model of breast cancer (BC). Also, a highly significant increase in IRAP activity has been found in BC tissue from women patients. Here, we found no changes in circulating IRAP in premenopausal (preMP) women, but it increased significantly in postmenopausal (postMP) women not treated with neoadjuvant chemotherapy (NACH). However, in women treated with NACH, IRAP activity increased in both preMP and postMP women. Two years of follow-up indicated lower levels of IRAP activity in untreated preMP women, but a return to control levels in untreated postMP women, while IRAP activity returned to control levels in women treated with NACH. Circulating oxytocin decreased in both preMP and postMP women during the follow-up period. Differences in Oxytocin appeared between preMP and postMP women treated with NACH, but not in women who were not treated with NACH. On the contrary, circulating vasopressin increased in untreated and treated preMP and postMP women, with most of the differences related to the hormonal status as well as the neoadjuvant treatment during the two year follow-up We propose that IRAP is involved in mechanisms related not only to oxytocin and/or vasopressin regulation, but also to the local mammary RAS through AngIV and its role in glucose transportation through the IRAP/GLUT4 system. MDPI 2020-11-04 /pmc/articles/PMC7694176/ /pubmed/33158090 http://dx.doi.org/10.3390/cancers12113252 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ramírez-Expósito, María Jesús
Dueñas-Rodríguez, Basilio
Carrera-González, María Pilar
Navarro-Cecilia, Joaquín
Martínez-Martos, Jose Manuel
Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin
title Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin
title_full Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin
title_fullStr Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin
title_full_unstemmed Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin
title_short Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin
title_sort insulin-regulated aminopeptidase in women with breast cancer: a role beyond the regulation of oxytocin and vasopressin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694176/
https://www.ncbi.nlm.nih.gov/pubmed/33158090
http://dx.doi.org/10.3390/cancers12113252
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