Leptin Promotes Glioblastoma

Lawrence, Johnathan E.; Cook, Nicholas; Rovin, Richard; Winn, Robert J.

doi:10.1155/2012/870807

Cited by 14 publications

(17 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These molecules are weakly expressed in non-malignant cells, but overexpressed in cancer cells in the colon [53,54], liver [55], brain [56,57] and breast [11,58,59,60]. Leptin and OB-R are expressed in more than 80% of breast cancer tissue [61] according to immunohistochemistry results in which only cancer cells were evaluated for antigen expression, however, the expression of leptin or OB-R in stroma was not determined.…”

Section: Leptin and Ob-r Expression And Signalingmentioning

confidence: 99%

Leptin’s Pro-Angiogenic Signature in Breast Cancer

Gonzalez-Perez

Lanier

Newman

2013

Cancers

View full text Add to dashboard Cite

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.

show abstract

Section: Leptin and Ob-r Expression And Signalingmentioning

confidence: 99%

Leptin’s Pro-Angiogenic Signature in Breast Cancer

Gonzalez-Perez

Lanier

Newman

2013

Cancers

View full text Add to dashboard Cite

show abstract

“…Leptin is an anti-apoptotic molecule in many cell types and its possible role in obesity-linked cancers originates from its known pro-angiogenic, pro-inflammatory and mitogenic activities. Furthermore, leptin was defined as a growth factor not only because of its proliferative activity but also due to its effect on cell motility and migration [65]. Leptin is overexpressed in at least 80% of cases of human skin melanoma [66], breast [67], ovarian [68] and prostate [69] cancers.…”

Section: Leptin Antagonists As Anticancer Agentsmentioning

confidence: 99%

“…More recently, attention has been given to the role of leptin in glioblastoma and is reviewed elsewhere (see ref. [65]). Though extensive in-vivo studies are still lacking and the information linking leptin to glioblastoma stems mainly from studies with glioma cell line C6 [88,89], the authors strongly suggest leptin's role not only in cell proliferation and inhibition of apoptosis but also in leptin-enhanced cell migration [90].…”

Section: Leptin Antagonists As Anticancer Agentsmentioning

confidence: 99%

Novel Superactive Leptin Antagonists and their Potential Therapeutic Applications

Gertler¹,

Elinav

2014

CPD

View full text Add to dashboard Cite

Random mutagenesis of mouse leptin antagonist (L39A/D40A/F41) followed by selection of high-affinity mutants by yeastsurface display indicated that replacing residue D23 with a non-negatively charged amino acid (most specifically with Leu) leads to dramatically enhanced affinity of leptin toward LEPR leading to development of superactive mouse, human, ovine and rat leptin antagonists (D23L/L39A/D40A/F41A). Superactive leptin antagonist mutants of mouse, human, rat or ovine leptins were developed in our laboratory, expressed in E. coli, refolded and purified to homogeneity as monomeric proteins. Pegylation of leptin antagonists resulted in potent and effective long-acting reagents suitable for in vivo studies or therapies. In the present review we explain the mechanism of leptin inhibition and summarize the possible use of leptin antagonists as possible leptin blockers in various human pathologies such as antiinflammatory and anti-autoimmune diseases, uremic cachexia, and cancer. We also suggest the use of leptin antagonists as research reagents for creation of a novel, fast and reversible model of T2DM in mice.

show abstract

“…Leptin is an anti-apoptotic molecule in many cell types and its possible role in obesity-linked cancers originates from its known pro-angiogenic, pro-inflammatory and mitogenic activities. Furthermore, leptin was defined as a growth factor not only because of its proliferative activity but also due to its effect on cell motility and migration (34). Leptin is overexpressed in at least 80% of cases of human skin melanoma (35), breast (36), ovarian (37) and prostate (38) cancers.…”

Section: Leptin Antagonists As Anticancer Agentsmentioning

confidence: 99%

Development of superactive leptin antagonists and their potential use in research and medicine

Gertler

2012

Adipobiology

View full text Add to dashboard Cite

superactive leptin antagonists (D23l/l39a/D40a/F41a), mutants of mouse, human, rat or ovine leptons, were developed in our laboratory, expressed in E. coli, refolded and purified to homogeneity as monomeric proteins. pegylation of leptin antagonists resulted in a potent and effective long-acting reagents suitable for in vivo studies. In the present review we summarize the possible use of leptin antagonists as (i) research reagents in the study of bone development, autoimmune diseases, metabolic syndrome and type 2 diabetes mellitus (T2Dm) with particular emphasis on creation of a novel, fast and reversible model of metabolic syndrome and T2Dm in mice, and (ii) possible leptin blockers in various human pathologies such as uremic cachexia, anti-inflammatory and anti-autoimmune diseases, and cancer. In conclusion, the recognition and mutagenesis of D23l of previously developed leptin antagonists (l39a/D40a/F41a) enabled construction of novel compounds that induce potent and reversible central and peripheral leptin deficiency.

show abstract

Leptin Promotes Glioblastoma

Cited by 14 publications

References 83 publications

Leptin’s Pro-Angiogenic Signature in Breast Cancer

Leptin’s Pro-Angiogenic Signature in Breast Cancer

Novel Superactive Leptin Antagonists and their Potential Therapeutic Applications

Development of superactive leptin antagonists and their potential use in research and medicine

Contact Info

Product

Resources

About