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The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression
Adipokines represent likely candidates to mediate the increased breast cancer risk and the enhanced progression associated with obesity. Other contributors to obesity-related cancer progression are insulin/IGF-1 pathways and hormones. Among these, the adipokine leptin is the most intensively studied...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245002/ https://www.ncbi.nlm.nih.gov/pubmed/25505738 http://dx.doi.org/10.3389/fonc.2014.00340 |
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author | Andò, Sebastiano Barone, Ines Giordano, Cinzia Bonofiglio, Daniela Catalano, Stefania |
author_facet | Andò, Sebastiano Barone, Ines Giordano, Cinzia Bonofiglio, Daniela Catalano, Stefania |
author_sort | Andò, Sebastiano |
collection | PubMed |
description | Adipokines represent likely candidates to mediate the increased breast cancer risk and the enhanced progression associated with obesity. Other contributors to obesity-related cancer progression are insulin/IGF-1 pathways and hormones. Among these, the adipokine leptin is the most intensively studied in both metabolism in general and in cancer due to the fact that leptin levels increase in proportion of fat mass. Leptin is primarily synthesized from adipocytes but it is also produced by other cells including fibroblasts. In this latter case, it has been well demonstrated how cancer-associated fibroblasts express leptin receptor and secrete leptin, which sustains a short autocrine loop and is able to target tumor epithelial cells enhancing breast cancer cell motility and invasiveness. In addition, it has been reported that leptin may induce breast cancer to undergo a transition from epithelial to spindle-like mesenchymal morphology, activating the signaling pathways devoted to the EMT. Thus, it emerges how leptin may play a crucial role in mediating malignant cell and tumor microenvironment interactions. Here, we present an overview of the role of leptin in breast cancer, covering the following topics: (1) leptin as an amplifier of estrogen signaling in tumor epithelial cells contributing to the promotion of carcinogenesis; (2) leptin as a crucial player in mediating tumor-stroma interaction and influencing EMT-linked mechanisms, that may sustain breast cancer growth and progression; (3) leptin and leptin receptor targeting as novel therapeutic strategies for breast cancer treatment. |
format | Online Article Text |
id | pubmed-4245002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-42450022014-12-10 The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression Andò, Sebastiano Barone, Ines Giordano, Cinzia Bonofiglio, Daniela Catalano, Stefania Front Oncol Oncology Adipokines represent likely candidates to mediate the increased breast cancer risk and the enhanced progression associated with obesity. Other contributors to obesity-related cancer progression are insulin/IGF-1 pathways and hormones. Among these, the adipokine leptin is the most intensively studied in both metabolism in general and in cancer due to the fact that leptin levels increase in proportion of fat mass. Leptin is primarily synthesized from adipocytes but it is also produced by other cells including fibroblasts. In this latter case, it has been well demonstrated how cancer-associated fibroblasts express leptin receptor and secrete leptin, which sustains a short autocrine loop and is able to target tumor epithelial cells enhancing breast cancer cell motility and invasiveness. In addition, it has been reported that leptin may induce breast cancer to undergo a transition from epithelial to spindle-like mesenchymal morphology, activating the signaling pathways devoted to the EMT. Thus, it emerges how leptin may play a crucial role in mediating malignant cell and tumor microenvironment interactions. Here, we present an overview of the role of leptin in breast cancer, covering the following topics: (1) leptin as an amplifier of estrogen signaling in tumor epithelial cells contributing to the promotion of carcinogenesis; (2) leptin as a crucial player in mediating tumor-stroma interaction and influencing EMT-linked mechanisms, that may sustain breast cancer growth and progression; (3) leptin and leptin receptor targeting as novel therapeutic strategies for breast cancer treatment. Frontiers Media S.A. 2014-11-26 /pmc/articles/PMC4245002/ /pubmed/25505738 http://dx.doi.org/10.3389/fonc.2014.00340 Text en Copyright © 2014 Andò, Barone, Giordano, Bonofiglio and Catalano. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Andò, Sebastiano Barone, Ines Giordano, Cinzia Bonofiglio, Daniela Catalano, Stefania The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression |
title | The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression |
title_full | The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression |
title_fullStr | The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression |
title_full_unstemmed | The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression |
title_short | The Multifaceted Mechanism of Leptin Signaling within Tumor Microenvironment in Driving Breast Cancer Growth and Progression |
title_sort | multifaceted mechanism of leptin signaling within tumor microenvironment in driving breast cancer growth and progression |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245002/ https://www.ncbi.nlm.nih.gov/pubmed/25505738 http://dx.doi.org/10.3389/fonc.2014.00340 |
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