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Leptin’s Pro-Angiogenic Signature in Breast Cancer

Obesity is linked to increased incidence of breast cancer. The precise causes and mechanisms of these morbid relationships are unknown. Contradictory data on leptin angiogenic actions have been published. However, accumulating evidence would suggest that leptin’s pro-angiogenic effects in cancer pla...

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Autores principales: Gonzalez-Perez, Ruben Rene, Lanier, Viola, Newman, Gale
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795383/
https://www.ncbi.nlm.nih.gov/pubmed/24202338
http://dx.doi.org/10.3390/cancers5031140
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author Gonzalez-Perez, Ruben Rene
Lanier, Viola
Newman, Gale
author_facet Gonzalez-Perez, Ruben Rene
Lanier, Viola
Newman, Gale
author_sort Gonzalez-Perez, Ruben Rene
collection PubMed
description Obesity is linked to increased incidence of breast cancer. The precise causes and mechanisms of these morbid relationships are unknown. Contradictory data on leptin angiogenic actions have been published. However, accumulating evidence would suggest that leptin’s pro-angiogenic effects in cancer play an essential role in the disease. Leptin, the main adipokine secreted by adipose tissue, is also abnormally expressed together with its receptor (OB-R) by breast cancer cells. Leptin induces proliferation and angiogenic differentiation of endothelial cells upregulates VEGF/VEGFR2 and transactivates VEGFR2 independent of VEGF. Leptin induces two angiogenic factors: IL-1 and Notch that can increase VEGF expression. Additionally, leptin induces the secretion and synthesis of proteases and adhesion molecules needed for the development of angiogenesis. Leptin’s paracrine actions can further affect stromal cells and tumor associated macrophages, which express OB-R and secrete VEGF and IL-1, respectively. A complex crosstalk between leptin, Notch and IL-1 (NILCO) that induces VEGF/VEGFR2 is found in breast cancer. Leptin actions in tumor angiogenesis could amplify, be redundant and/or compensatory to VEGF signaling. Current failure of breast cancer anti-angiogenic therapies emphasizes the necessity of targeting the contribution of other pro-angiogenic factors in breast cancer. Leptin’s impact on tumor angiogenesis could be a novel target for breast cancer, especially in obese patients. However, more research is needed to establish the importance of leptin in tumor angiogenesis. This review is focused on updated information on how leptin could contribute to tumor angiogenesis.
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spelling pubmed-37953832013-10-21 Leptin’s Pro-Angiogenic Signature in Breast Cancer Gonzalez-Perez, Ruben Rene Lanier, Viola Newman, Gale Cancers (Basel) Review Obesity is linked to increased incidence of breast cancer. The precise causes and mechanisms of these morbid relationships are unknown. Contradictory data on leptin angiogenic actions have been published. However, accumulating evidence would suggest that leptin’s pro-angiogenic effects in cancer play an essential role in the disease. Leptin, the main adipokine secreted by adipose tissue, is also abnormally expressed together with its receptor (OB-R) by breast cancer cells. Leptin induces proliferation and angiogenic differentiation of endothelial cells upregulates VEGF/VEGFR2 and transactivates VEGFR2 independent of VEGF. Leptin induces two angiogenic factors: IL-1 and Notch that can increase VEGF expression. Additionally, leptin induces the secretion and synthesis of proteases and adhesion molecules needed for the development of angiogenesis. Leptin’s paracrine actions can further affect stromal cells and tumor associated macrophages, which express OB-R and secrete VEGF and IL-1, respectively. A complex crosstalk between leptin, Notch and IL-1 (NILCO) that induces VEGF/VEGFR2 is found in breast cancer. Leptin actions in tumor angiogenesis could amplify, be redundant and/or compensatory to VEGF signaling. Current failure of breast cancer anti-angiogenic therapies emphasizes the necessity of targeting the contribution of other pro-angiogenic factors in breast cancer. Leptin’s impact on tumor angiogenesis could be a novel target for breast cancer, especially in obese patients. However, more research is needed to establish the importance of leptin in tumor angiogenesis. This review is focused on updated information on how leptin could contribute to tumor angiogenesis. MDPI 2013-09-06 /pmc/articles/PMC3795383/ /pubmed/24202338 http://dx.doi.org/10.3390/cancers5031140 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Gonzalez-Perez, Ruben Rene
Lanier, Viola
Newman, Gale
Leptin’s Pro-Angiogenic Signature in Breast Cancer
title Leptin’s Pro-Angiogenic Signature in Breast Cancer
title_full Leptin’s Pro-Angiogenic Signature in Breast Cancer
title_fullStr Leptin’s Pro-Angiogenic Signature in Breast Cancer
title_full_unstemmed Leptin’s Pro-Angiogenic Signature in Breast Cancer
title_short Leptin’s Pro-Angiogenic Signature in Breast Cancer
title_sort leptin’s pro-angiogenic signature in breast cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795383/
https://www.ncbi.nlm.nih.gov/pubmed/24202338
http://dx.doi.org/10.3390/cancers5031140
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