The relationship between stage and tumor type and serum leptin level and leptin expression on tumor tissue in lung cancer

Duru, Serap; Sönmez, Zeynep; Kont, Yasemin Saygideğer; Sever, Ozlem Salman; Önal, Binnur; Ardıç, Sadık

doi:10.5578/tt.2478

Cited by 3 publications

(5 citation statements)

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“…Leptin is widely recognized as a cytokine, pleiotropic hormone, and an obesity-associated adipokine that upon binding to its leptin receptor, regulates energy metabolism and appetite 12 – 14 . More recently, expression of both leptin and its receptor has been documented in cell types besides adipocytes that include cancer cells, suggesting a possible role in cancer signaling 12 , 15 – 18 , 21 – 23 . Both leptin and its receptor were found to be expressed in NSCLC at higher levels than in normal lung tissues 15 , 18 – 23 , 42 , 47 and led to proliferation and antiapoptotic functions 19 , 42 , 47 .…”

Section: Discussionmentioning

confidence: 99%

“…More recently, expression of both leptin and its receptor has been documented in cell types besides adipocytes that include cancer cells, suggesting a possible role in cancer signaling 12 , 15 – 18 , 21 – 23 . Both leptin and its receptor were found to be expressed in NSCLC at higher levels than in normal lung tissues 15 , 18 – 23 , 42 , 47 and led to proliferation and antiapoptotic functions 19 , 42 , 47 . Expression levels of leptin were higher in four NSCLC cell lines, including A549 and H1299, than in normal control lung cells 42 , 48 .…”

Section: Discussionmentioning

confidence: 99%

“…More recently, however, leptin was shown to be synthesized and secreted by several non-adipose tissues including lung tissue, and both leptin and its receptors are considered to play a role in the development and progression of a variety of tumors 15 , 17 . The leptin receptor, a type 1 cytokine receptor, has been shown to be highly abundant in a broad range of cancer types with an important role in the escalation and pathogenesis of many tumors via activation of signaling cascades crucial for cancer cell growth 16 – 23 . Leptin was shown to be upregulated in lung tumors compared with normal lung increasing their growth, proliferation, and metastasis, with anti-apoptotic functions 15 , 17 , 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

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The role of leptin in regulation of the soluble amyloid precursor protein α (sAPPα) levels in lung cancer cell media

Haddad,

Khalil,

Al Khashali

et al. 2024

Sci Rep

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Previously, we found that the levels of soluble amyloid precursor protein α (sAPPα) are regulated, in part, by acetylcholinesterase (AChE) in human A549 (p53 wild-type) and H1299 (p53-null) NSCLC cell lines. In this study, we found regulation of sAPPα levels in the media by leptin, a widely recognized obesity-associated adipokine that has recently been shown to play a possible role in cancer signaling. Increased levels of sAPPα, that were accompanied by lower Aβ40/42 levels in the media of A549 and H1299 cells, were detected upon cell incubation with leptin. Conversely, knockdown of leptin or its receptor led to reduced levels of sAPPα and increased levels of Aβ40/42 in the media of A549 and H1299 cells, suggesting that leptin likely shifts APP processing toward the non-amyloidogenic pathway. A549 cell treatment with leptin increased acetylcholine levels and blocked the activities of AChE and p53. Treatment with leptin resulted in increased activation of PKC, ERK1/2, PI3K, and the levels of sAPPα, effects that were reversed by treatment with kinase inhibitors and/or upon addition of AChE to A549 and H1299 cell media. Cell viability increased by treatment of A549 and H1299 cells with leptin and decreased upon co-treatment with AChE and/or inhibitors targeting PKC, ERK1/2, and PI3K. This study is significant as it provides evidence for a likely carcinogenic role of leptin in NSCLC cells via upregulation of sAPPα levels in the media, and highlights the importance of targeting leptin as a potential therapeutic strategy for NSCLC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The role of leptin in regulation of the soluble amyloid precursor protein α (sAPPα) levels in lung cancer cell media

Haddad,

Khalil,

Al Khashali

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…However, a recent meta-analysis showed that plasma leptin concentrations had no significant effect on long-term outcome in patients with lung cancer (18). Several studies have shown that leptin and its receptor are overexpressed in NSCLC, and leptin protein is mainly expressed in the cytoplasm of epithelial cells (cancer cells) and the expression level is higher than that of normal lung tissues, while Ob-R is expressed in both cytoplasm and the membrane of tumor cells (18,19,(21)(22)(23)(24)(25)(26)(27). Thus, whether leptin promotes the proliferation of lung cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Autocrined leptin promotes proliferation of non-small cell lung cancer (NSCLC) via PI3K/AKT and p53 pathways

Wang¹,

Zhou²,

Li³

et al. 2021

Ann Transl Med

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Background: Circulating leptin can directly act on tumor cells. However, a recent meta-analysis showed that plasma leptin concentration had no significant effect on the survival of lung cancer patients. So does Leptin have an effect on lung cancer? Or there may be other factors that influence the effect.Methods: Genome sequencing database Oncomine was searched to learn the differential expression of leptin between tumors and normal lungs. Fresh tumor specimens and paired normal lung tissue from six lung adenocarcinoma patients were collected, and validate the expression level of leptin. Clinicopathological information and tumor slices from 60 non-small cell lung cancer (NSCLC) patients were analyzed to evaluate the prognostic value of autocrined leptin. Whole genome sequencing data from the cancer genome atlas (TCGA) was analyzed to predict the underlying mechanism of leptin regulating tumor proliferation.Finally, these findings were confirmed by using cell lines H1299, A549, H460, and H322 to explore the promoting effect and mechanism of leptin on cell proliferation in vitro.Results: Five datasets in Oncomine reported the expression of the LEP gene in NSCLC, and 4 datasets showed that leptin was up-regulated in tumors compared with normal lungs. Leptin was also overexpressed in 5 out of 6 clinical lung adenocarcinoma specimens. The analysis of the 60 NSCLC patients revealed that autocrined leptin could serve as an auxiliary prognostic factor, and a higher expression of leptin indicated a higher survival risk. Gene set enrichment analysis (GSEA) showed that the PI3K/AKT/mTOR signaling pathway was positively enriched when the LEP gene was highly expressed, while the P53 signaling pathway was negatively enriched. Leptin promoted cell cycle and clone formation in H1299 and A549 cells, upregulation or down-regulation of leptin in these two cell lines led to enhanced or declined proliferation.Finally, it was confirmed that the PI3K/AKT/mTOR signaling pathway was positively regulated by leptin expression, while the P53 signaling pathway was negatively regulated.Conclusions: Autocrined leptin was observed in majority of NSCLC tissue, which could serve as an auxiliary prognostic factor for NSCLC patients. Autocrined leptin had a promoting effect on the proliferation of NSCLC cells, which probably positively regulating the PI3K/AKT/mTOR signaling pathway and negatively regulate the P53 signaling pathway.

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“…Furthermore, leptin is a pleiotropic hormone with proliferative and anti-apoptotic roles. Several studies over the past few years have suggested that leptin/leptin receptor dysregulation is important in the development of various types of malignancy, including lung (11), breast (12), gastric (13) and thyroid cancer (14). However, the anti-apoptotic effect and specific mechanisms underlying the role of leptin in liver cancer remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Human leptin protein activates the growth of HepG2 cells by inhibiting PERK-mediated ER stress and apoptosis

Xiong

Zhang

Liu

et al. 2014

Molecular Medicine Reports

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Current treatment modalities for various types of hepatic cancer, which has an increasing incidence rate, are inadequate and novel therapies are required. Therefore, identifying targets for liver cancer is becoming increasingly valuable to develop novel methods for therapy. The aim of the present study was to examine the growth activation mechanism of the leptin protein in the liver cancer cell line HepG2. The effects of the leptin protein on cell death were investigated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide analysis. DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis were also performed to detect cell apoptosis. The expression of leptin and three endoplasmic reticulum (ER) stress unfolded protein response (UPR) proteins, including activating transcription factor 6, phosphorylated‑PKR‑like ER kinase (p‑PERK) and inositol requiring protein 1, were investigated for the examination of ER stress. The mRNA UPR proteins were also detected by reverse transcription polymerase chain reaction. The apoptosis‑associated caspase 12 and C/EBP homologous protein (CHOP) was detected by western blot analysis. The expression of or incubation with the leptin protein was able to activate cell growth and inhibit cell death and apoptosis. In cells that expressed leptin or were incubated with leptin protein (pep-LPT), cisplatin‑induced ER stress‑associated mRNA transcription and protein activation were inhibited. Levels of the ER stress UPR pathway protein, PERK, increased significantly in leptin‑silenced cells when treated with cisplatin as compared with those in the leptin‑expressing or pep-LPT cells. Furthermore, caspase 12 activation was inhibited in ex‑LPT, pep‑LPT and HepG2 cells. In conclusion, human leptin protein is involved in promoting the proliferation of HepG2 cells through inhibiting the ER stress‑associated apoptotic pathway. The PERK UPR pathway and the apoptotic factor caspase 12 were found to be involved in the inhibition of apoptosis and enhancement of proliferation.

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The relationship between stage and tumor type and serum leptin level and leptin expression on tumor tissue in lung cancer

Cited by 3 publications

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The role of leptin in regulation of the soluble amyloid precursor protein α (sAPPα) levels in lung cancer cell media

The role of leptin in regulation of the soluble amyloid precursor protein α (sAPPα) levels in lung cancer cell media

Autocrined leptin promotes proliferation of non-small cell lung cancer (NSCLC) via PI3K/AKT and p53 pathways

Human leptin protein activates the growth of HepG2 cells by inhibiting PERK-mediated ER stress and apoptosis

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