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Cancers 2013, 5(3), 1140-1162; doi:10.3390/cancers5031140
Review

Leptin’s Pro-Angiogenic Signature in Breast Cancer

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Received: 5 July 2013; in revised form: 23 July 2013 / Accepted: 30 August 2013 / Published: 6 September 2013
(This article belongs to the Special Issue Tumour Angiogenesis)
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Abstract: 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.
Keywords: leptin; breast cancer; tumor angiogenesis; Notch; IL-1; VEGF; VEGFR2; NILCO; leptin peptide receptor antagonist leptin; breast cancer; tumor angiogenesis; Notch; IL-1; VEGF; VEGFR2; NILCO; leptin peptide receptor antagonist
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Gonzalez-Perez, R.R.; Lanier, V.; Newman, G. Leptin’s Pro-Angiogenic Signature in Breast Cancer. Cancers 2013, 5, 1140-1162.

AMA Style

Gonzalez-Perez RR, Lanier V, Newman G. Leptin’s Pro-Angiogenic Signature in Breast Cancer. Cancers. 2013; 5(3):1140-1162.

Chicago/Turabian Style

Gonzalez-Perez, Ruben R.; Lanier, Viola; Newman, Gale. 2013. "Leptin’s Pro-Angiogenic Signature in Breast Cancer." Cancers 5, no. 3: 1140-1162.



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