Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation

Fazeli, Mehdi; Zarkesh-Esfahani, Hamid; Wu, Zida; Maamra, M; Bidlingmaier, Martin; Pockley, A. Graham; Watson, P.; Matarese, Giuseppe; Strasburger, Christian J.; Ross, R. J. M.

doi:10.1016/j.jim.2006.03.011

Cited by 57 publications

(42 citation statements)

References 27 publications

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“…Gonzalez et al (2009) inhibited growth of murine mammary cancer cell and xenograft tumor model of human breast cancer cell lines by leptin peptide antagonist (Gonzalez et al, 2009). In addition, leptin analog mimicking its action (Peters et al, 2007) and anti-leptin receptor monoclonal antibody (Fazeli et al, 2006) are also other approaches for interfering with the leptin function. In the other studies, administrations of some compounds including b3-adrenoreceptor agonist, conjugated linoleic Acid, isoflavone, resveratrol and bitter melon lead to decreased secretion and lower levels of serum leptin (Ray and Cleary, 2010).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Leptin and Leptin Receptor Gene Expression by Silibinin-Curcumin Combination

Nejati-Koshki¹,

Akbarzadeh²,

Pourhasan-Moghaddam³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Leptin and its receptor are involved in breast carcinogenesis as mitogenic factors. Therefore, they could be considered as targets for breast cancer therapy. Expression of the leptin receptor gene could be modulated by leptin secretion. Silibinin and curcumin are herbal compounds with anti-cancer activity against breast cancer. The aim of this study was to assess their potential to inhibit of expression of the leptin gene and its receptor and leptin secretion. Cytotoxic effects of the two agents on combination on T47D breast cancer cells was investigated by MTT assay test after 24h treatment. With different concentrations the levels of leptin, leptin receptor genes expression were measured by reverse-transcription real-time PCR. Amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. The silibinin and curcumin combination inhibited growth of T47D cells in a dose dependent manner. There were also significant difference between control and treated cells in leptin expression and the quantity of secreted leptin with a relative decrease in leptin receptor expression. In conclusion, these herbal compounds inhibit the expression and secretion of leptin and it could probably be used as drug candidates for breast cancer therapy through leptin targeting in the future.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Leptin and Leptin Receptor Gene Expression by Silibinin-Curcumin Combination

Nejati-Koshki¹,

Akbarzadeh²,

Pourhasan-Moghaddam³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…For in vitro blocking experiments, human LepR-neutralizing mAb 9F8 (Fazeli et al 2006), kindly provided by Prof. Richard Ross (University of Sheffield, UK), was used at a final concentration of 25 ng/ml. Human recombinant leptin (rleptin; R&D Systems, Minneapolis, MN, USA) was used at different concentrations (1, 10, and 100 ng/ml).…”

Section: Reagentsmentioning

confidence: 99%

Cellular and molecular crosstalk between leptin receptor and estrogen receptor-α in breast cancer: molecular basis for a novel therapeutic setting

Fusco¹,

Galgani²,

Procaccini³

et al. 2010

Endocrine-Related Cancer

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Obesity is associated with an increased risk of breast cancer. A number of adipocytokines are increased in obesity causing low-level chronic inflammation associated with an increased risk of tumors. The adipocytokine leptin shows profound anti-obesity and pro-inflammatory activities. We have hypothesized that in common obesity, high circulating leptin levels might contribute to an increased risk of breast cancer by affecting mammary cell proliferation and survival. Leptin exerts its activity not only through leptin receptor (LepR), but also through crosstalk with other signaling systems implicated in tumorigenesis. In this study, we focused our attention on the relationship between the leptin/LepR axis and the estrogen receptor-a (ERa). To this aim, we utilized two human breast cancer cell lines, one ERa-positive cell line (MCF 7) and the other ERa-negative cell line (MDA-MB 231). We observed that the two cell lines had a different sensitivity to recombinant leptin (rleptin): on MCF 7 cells, rleptin induced a strong phosphorylation of the signal transducer and activator of transcription (STAT) 3 and of the extracellular related kinase 1/2 pathways with an increased cell viability and proliferation associated with an increased expression of ERa receptor. This response was not present in the MDA-MB 231 cells. The effects induced by leptin were lost when LepR was neutralized using either a monoclonal inhibitory antibody to LepR or LepR genesilencing siRNA. These data suggest that there is a bidirectional communication between LepR and ERa, and that neutralization and/or inactivation of LepR inhibits proliferation and viability of human breast cancer cell lines. This evidence was confirmed by ex vivo studies, in which we analyzed 33 patients with breast cancer at different stages of disease, and observed that there was a statistically significant correlation between the expression of LepR and ERa. In conclusion, this study suggests a crosstalk between LepR and ERa, and could envisage novel therapeutic settings aimed at targeting the LepR in breast cancers.

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“…4) It has been implicated in a variety of physiologic functions, such as development of embryos, 5) olfaction, 6) immunology, 7) angiogenesis, 8) and endocrine actions, renal and pulmonary functions 9) and reproduction. 10) Thus, despite great progress in the investigation of leptin-mediated regulation, these processes await further clarification.…”

mentioning

confidence: 99%

Leptin Promotes Proliferation and Inhibits Differentiation in Porcine Skeletal Myoblasts

Luo

Zhang

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation

Cited by 57 publications

References 27 publications

Inhibition of Leptin and Leptin Receptor Gene Expression by Silibinin-Curcumin Combination

Inhibition of Leptin and Leptin Receptor Gene Expression by Silibinin-Curcumin Combination

Cellular and molecular crosstalk between leptin receptor and estrogen receptor-α in breast cancer: molecular basis for a novel therapeutic setting

Leptin Promotes Proliferation and Inhibits Differentiation in Porcine Skeletal Myoblasts

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