Serum Levels of Leptin in Multiple Myeloma Patients and Its Relation to Angiogenic and Inflammatory Cytokines

Alexandrakis, M.G.; Passam, Freda; Sfiridaki, Aekaterini; Pappa, Constantina A.; Moschandrea, J.; Kandidaki, E.; Tsirakis, George; Kyriakou, Despina

doi:10.1177/172460080401900107

Cited by 25 publications

(17 citation statements)

References 32 publications

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“…Few studies [11, 17, 24–26] have investigated the effects of leptin in hematological tumors and found that leptin modestly promotes proliferation of myeloma cell lines, and reduces chemotherapy induced apoptosis in myeloma cell lines, which are in accordance with our results. In addition, Leptin was correlated with ISS stage in patients with multiple myeloma.…”

Section: Discussionsupporting

confidence: 91%

“…We found that mature adipocytes could directly stimulate proliferation, accelerate cell cycle, and up-regulate cell cycle related proteins in multiple myeloma cells when cultured together. Several studies [17, 25, 26] have revealed that adipocytes secreted leptin could help tumor cells to proliferate, chemo-resistant, and metastasis via activating pro-tumor pathways. After adding anti-leptin related receptor antibodies, the proliferation of myeloma cells was inhibited, indicating leptin and its receptors were responsible for the pro-tumor effect of adipocytes.…”

Section: Discussionmentioning

confidence: 99%

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Adipocytes secreted leptin is a pro-tumor factor for survival of multiple myeloma under chemotherapy

Wen

Cao

et al. 2016

Oncotarget

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Accumulating evidences have shown that adipokines secreted from adipocytes contributes to tumor development, especially leptin. However, underlying mechanisms remain unclear. This study aims to explore the effect of leptin on development and chemoresistance in multiple myeloma cells and the potential mechanism. Analysis of levels of adipokines including leptin and adiponectin in 28 multiple myeloma patients identified significantly higher leptin compared with 28 normal controls(P < 0.05), and leptin level was positively correlated with clinical stage, IgG, ER, and ß2MG. Next, by using co-culture system of myeloma and adipocytes, and pharmacologic enhancement of leptin, we found that increased growth of myeloma cells and reduced toxicity of bortezomib were best observed at 50 ng/ml of leptin, along with increased expression of cyclinD1, Bcl-2 and decreased caspase-3 expression. We also found that phosphorylated AKT and STAT3 but not the proteins expression reached peak after 1h and 6h treatment of leptin, respectively. By using AG490, an agent blocking the phosphorylation of AKT and ERK, the proliferation of myeloma cells was inhibited, as well as the phosphorylation of AKT and STAT3, even adding leptin. Taken together, our study demonstrated that up-regulated leptin could stimulate proliferation of myeloma and reduce the anti-tumor effect of chemotherapy possibly via activating AKT and STAT3 pathways, and leptin might be one of the potential therapeutic targets for treating myeloma.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Adipocytes secreted leptin is a pro-tumor factor for survival of multiple myeloma under chemotherapy

Wen

Cao

et al. 2016

Oncotarget

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“…Although adiponectin was a significant predictor for MM risk, we haven't been able to find either a significant association between adiponectin levels and MM prognostic stages or a significant relation between adiponectin levels and prognostic biological parameters such as CRP [1,30], We have also found that MM patients tend to have higher mean leptin levels than controls by univariate analysis, which may reflect their higher degree of obesity. This is in agreement with two previous studies examining much fewer patients (14 and 62 patients) [25,26]. We also report herein that after adjusting for age, gender, and BMI, as well as for multiple comparisons performed, serum leptin levels weren't significantly different between MM patients and controls.…”

Section: Discussionsupporting

confidence: 95%

“…Two previous studies with small number of cases have examined leptin in association with MM [25,26]. No previous study has focused on adiponectin or resistin as predictors of MM and no prior study has explored simultaneously whether adiponectin, leptin, and/ or resistin are associated with MM.…”

Section: Introductionmentioning

confidence: 98%

Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case–control study

Dalamaga

Karmaniolas

Panagiotou

et al. 2008

Cancer Causes Control

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Accumulating evidence supports a role for obesity in the etiology of multiple myeloma (MM). The distinct possibility exists that obesity may be linked to MM through altered adipokine secretion and circulating levels, one of which, adiponectin, has a protective role in several malignancies, including leukemia. In this case-control study, we investigated the role of serum adiponectin, resistin, and leptin levels in the etiopathogenesis of MM and we explored their association with several established prognostic factors. Seventy three patients with incident, histologically confirmed MM and 73 controls matched on gender and age were studied between 2001 and 2007, and blood samples were collected. Serum adiponectin, leptin, resistin, as well as MM prognostic parameters were determined. Statistical analysis of the data was performed using univariate and multivariate analyses. Lower serum adiponectin and resistin levels were associated with higher risk of MM by bivariate analysis and after adjusting for age, gender, BMI, and serum levels of leptin (p < 0.0001). Adiponectin may have a protective role in MM, whereas leptin was not associated with risk for MM at a comparable level of significance and resistin levels may be decreased via a compensatory mechanism. Further studies are needed to confirm these associations and to explore the mechanisms underlying adiponectin's role in MM and plasma cell dyscrasias.

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“…Более того, содержание этого адипокина в крови прямо коррелирует с уровнями иммуноглобулина класса G (IgG) и β 2 -микроглобулина, содержанием плазматических клеток в костном мозге и стадией заболевания (5,34 ± 1,9 нг/мл при I-II стадиях и 7,93 ± 3,38 нг/мл при III стадии). Следует отметить, что содержание лептина в крови больных ММ достоверно снижается после проведения химиотерапии [42]. У больных ММ отмечается повышение содержания в сыворотке крови другого адипокина -хемерина [43].…”

Section: влияние адипоцитов костного мозга на миеломные клеткиunclassified

Bone marrow adipocytes and multiple myeloma

Фильченков

2019

Onkogematologiâ

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Multiple myeloma originating from clonal proliferation of plasma cells in the bone marrow is one of the most prevalent hematological malignancies worldwide. The pathogenetic mechanisms of multiple myeloma are far from being elucidated. Nevertheless, it is known that the adipocytes as the prevalent cellular component of bone marrow microenvironment contribute significantly to multiple myeloma growth and progression. The review discloses the recent data on the interactions between bone marrow adipocytes and myeloma cells, hematopoietic stemcells, hematopoietic progenitor cells, mesenchimal stem cells, osteoblasts, osteoclasts, endothelial cells, and cells of immune system. Also, the review places special emphasis on bone marrow adipocyte-produced adipokines, growth factors, cytokines, chemokines, and fatty acids providing the conditions for the preferential growth and migration of malignant plasma cells and contributing to hematopoiesis supression, bone tissue resorption, angiogenesis activation and immunosuppression.

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Serum Levels of Leptin in Multiple Myeloma Patients and Its Relation to Angiogenic and Inflammatory Cytokines

Abstract: Leptin serum levels do not reflect disease severity in MM. However, there seems to be a decrease in leptin following treatment, which may be associated with an alteration in the metabolic state or the chemokine milieu.

Cited by 25 publications

References 32 publications

Adipocytes secreted leptin is a pro-tumor factor for survival of multiple myeloma under chemotherapy

Adipocytes secreted leptin is a pro-tumor factor for survival of multiple myeloma under chemotherapy

Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case–control study

Bone marrow adipocytes and multiple myeloma

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