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Leptin's Pro-Angiogenic Signature in Breast Cancer.

Gonzalez-Perez RR, Lanier V, Newman G - Cancers (Basel) (2013)

Bottom Line: 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.However, more research is needed to establish the importance of leptin in tumor angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Dr. SW., Atlanta, GA 30310, USA. rgonzalez@msm.edu.

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.

No MeSH data available.


Related in: MedlinePlus

Relationships between pro-angiogenic effects of leptin signaling and breast neoplasms, vascularization, and endothelial cell function. Many signaling pathways show the connections between regulation, expression and binding of leptin, IL-1, adhesion molecules (ICAM and integrins), Notch, VEGF/VEGFR and MMPs and, their impact on vessel development and endothelial cell function, which are essential for breast neoplasm development. The summary of the data processed by the Program Studio 9 [19] and specific molecular and cellular relationships can be found in the supplementary material. Notes: ITG (integrins); ITGB1 (integrin β1); IL-1A and B (IL-1α and β); Lep (leptin); ICAM (CD54, intercellular adhesion molecule 1).
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cancers-05-01140-f002: Relationships between pro-angiogenic effects of leptin signaling and breast neoplasms, vascularization, and endothelial cell function. Many signaling pathways show the connections between regulation, expression and binding of leptin, IL-1, adhesion molecules (ICAM and integrins), Notch, VEGF/VEGFR and MMPs and, their impact on vessel development and endothelial cell function, which are essential for breast neoplasm development. The summary of the data processed by the Program Studio 9 [19] and specific molecular and cellular relationships can be found in the supplementary material. Notes: ITG (integrins); ITGB1 (integrin β1); IL-1A and B (IL-1α and β); Lep (leptin); ICAM (CD54, intercellular adhesion molecule 1).

Mentions: Pathway Studio 9 software (Ariadne Genomics, Rockville, MD, USA) was used to analyze in silico the potential targets of leptin pro-angiogenic signals and relationships to oncogenic factors [31], which could also impact breast cancer angiogenesis. Figure 2 depicts the various relationships between these molecules in breast cancer. One hundred sixty three relationships that include regulation, expression and binding of main leptin targets were detected in breast neoplasms. The proteins: leptin, IL-1, integrins, Notch and VEGF/VEGFR and vascularization and/or endothelial cell activation showed many relationships in breast neoplasms. These results are included in the supplemental material (S1). Among several leptin relationships with cell processes involving cancer and angiogenesis, changes of leptin/OB-R levels were related to breast cancer (38 references). Leptin/OB-R signaling was also related to regulation of vascularization and vasculogenesis (118 references), endothelial cell function, proliferation and vessel development (39 references). Numerous relationships between leptin/OB-R and angiogenic molecules (IL-1, Notch and VEGF/VEGFR) were detected (see Supplementary Material). The results of this analysis underline the many facets of leptin pro-angiogenic effects in cancer.


Leptin's Pro-Angiogenic Signature in Breast Cancer.

Gonzalez-Perez RR, Lanier V, Newman G - Cancers (Basel) (2013)

Relationships between pro-angiogenic effects of leptin signaling and breast neoplasms, vascularization, and endothelial cell function. Many signaling pathways show the connections between regulation, expression and binding of leptin, IL-1, adhesion molecules (ICAM and integrins), Notch, VEGF/VEGFR and MMPs and, their impact on vessel development and endothelial cell function, which are essential for breast neoplasm development. The summary of the data processed by the Program Studio 9 [19] and specific molecular and cellular relationships can be found in the supplementary material. Notes: ITG (integrins); ITGB1 (integrin β1); IL-1A and B (IL-1α and β); Lep (leptin); ICAM (CD54, intercellular adhesion molecule 1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3795383&req=5

cancers-05-01140-f002: Relationships between pro-angiogenic effects of leptin signaling and breast neoplasms, vascularization, and endothelial cell function. Many signaling pathways show the connections between regulation, expression and binding of leptin, IL-1, adhesion molecules (ICAM and integrins), Notch, VEGF/VEGFR and MMPs and, their impact on vessel development and endothelial cell function, which are essential for breast neoplasm development. The summary of the data processed by the Program Studio 9 [19] and specific molecular and cellular relationships can be found in the supplementary material. Notes: ITG (integrins); ITGB1 (integrin β1); IL-1A and B (IL-1α and β); Lep (leptin); ICAM (CD54, intercellular adhesion molecule 1).
Mentions: Pathway Studio 9 software (Ariadne Genomics, Rockville, MD, USA) was used to analyze in silico the potential targets of leptin pro-angiogenic signals and relationships to oncogenic factors [31], which could also impact breast cancer angiogenesis. Figure 2 depicts the various relationships between these molecules in breast cancer. One hundred sixty three relationships that include regulation, expression and binding of main leptin targets were detected in breast neoplasms. The proteins: leptin, IL-1, integrins, Notch and VEGF/VEGFR and vascularization and/or endothelial cell activation showed many relationships in breast neoplasms. These results are included in the supplemental material (S1). Among several leptin relationships with cell processes involving cancer and angiogenesis, changes of leptin/OB-R levels were related to breast cancer (38 references). Leptin/OB-R signaling was also related to regulation of vascularization and vasculogenesis (118 references), endothelial cell function, proliferation and vessel development (39 references). Numerous relationships between leptin/OB-R and angiogenic molecules (IL-1, Notch and VEGF/VEGFR) were detected (see Supplementary Material). The results of this analysis underline the many facets of leptin pro-angiogenic effects in cancer.

Bottom Line: 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.However, more research is needed to establish the importance of leptin in tumor angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Dr. SW., Atlanta, GA 30310, USA. rgonzalez@msm.edu.

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.

No MeSH data available.


Related in: MedlinePlus