Obesity and cancer: focus on leptin.
Adipokine
Cancer
Leptin
Obesity
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
12
02
2023
accepted:
12
05
2023
medline:
26
6
2023
pubmed:
25
5
2023
entrez:
25
5
2023
Statut:
ppublish
Résumé
Over the past decades, obesity has grown to epidemic proportions worldwide. It has been associated with an increased risk for different types of cancer. In addition, obesity has been associated with a poor prognosis, an increased risk of metastasis and mortality, and resistance to anti-cancer therapies. The pathophysiological mechanisms underlying the obesity-cancer connection have not yet been fully elucidated. However, this connection could result, at least in part, from the action of adipokines, whose levels are increased in obesity. Among these adipokines, evidence suggests leptin's critical role in linking obesity to cancer. In this review, we first summarize the current state of the literature regarding the implication of leptin in tumorigenic processes. Next, we focus on the effects of leptin on the anti-tumor immune response. Then, we discuss the influence of leptin on the efficiency of antineoplastic treatments and the development of tumor resistance. Finally, we highlight the use of leptin as a potential target for the prevention and treatment of cancer.
Identifiants
pubmed: 37227675
doi: 10.1007/s11033-023-08525-y
pii: 10.1007/s11033-023-08525-y
doi:
Substances chimiques
Adipokines
0
Antineoplastic Agents
0
Leptin
0
LEP protein, human
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
6177-6189Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Ng M, Fleming T, Robinson M et al (2014) Global, regional and national prevalence of overweight and obesity in children and adults 1980–2013: a systematic analysis. Lancet 384:766–781. https://doi.org/10.1016/S0140-6736(14)60460-8
doi: 10.1016/S0140-6736(14)60460-8
pubmed: 24880830
pmcid: 4624264
Kyrou I, Randeva HS, Tsigos C et al (2000) Clinical Problems Caused by Obesity. In: Feingold KR, Anawalt B, Boyce A et al (eds) Endotext. MDText.com Inc., South Dartmouth
O’Flanagan CH, Bowers LW, Hursting SD (2015) A weighty problem: metabolic perturbations and the obesity-cancer link. Horm Mol Biol Clin Investig 23:47–57. https://doi.org/10.1515/hmbci-2015-0022
doi: 10.1515/hmbci-2015-0022
pubmed: 26167982
pmcid: 4839982
Basen-Engquist K, Chang M (2011) Obesity and cancer risk: recent review and evidence. Curr Oncol Rep 13:71–76. https://doi.org/10.1007/s11912-010-0139-7
doi: 10.1007/s11912-010-0139-7
pubmed: 21080117
pmcid: 3786180
Barone I, Giordano C, Bonofiglio D et al (2016) Leptin, obesity and breast cancer: progress to understanding the molecular connections. Curr Opin Pharmacol 31:83–89. https://doi.org/10.1016/j.coph.2016.10.003
doi: 10.1016/j.coph.2016.10.003
pubmed: 27816025
Friedman JM (2010) A tale of two hormones. Nat Med 16:1100–1106. https://doi.org/10.1038/nm1010-1100
doi: 10.1038/nm1010-1100
pubmed: 20930753
Wauman J, Zabeau L, Tavernier J (2017) The leptin receptor complex: heavier than expected? Front Endocrinol. https://doi.org/10.3389/fendo.2017.00030
doi: 10.3389/fendo.2017.00030
Modzelewska P, Chludzińska S, Lewko J, Reszeć J (2019) The influence of leptin on the process of carcinogenesis. Contemp Oncol (Pozn) 23:63–68. https://doi.org/10.5114/wo.2019.85877
doi: 10.5114/wo.2019.85877
pubmed: 31316286
Gorska E, Popko K, Stelmaszczyk-Emmel A et al (2010) Leptin receptors. Eur J Med Res 15:50–54. https://doi.org/10.1186/2047-783X-15-S2-50
doi: 10.1186/2047-783X-15-S2-50
pubmed: 21147620
pmcid: 4360333
Frühbeck G (2006) Intracellular signalling pathways activated by leptin. Biochem J 393:7–20. https://doi.org/10.1042/BJ20051578
doi: 10.1042/BJ20051578
pubmed: 16336196
Ollberding NJ, Kim Y, Shvetsov YB et al (2013) Prediagnostic leptin, adiponectin, C-reactive protein and the risk of postmenopausal breast cancer. Cancer Prev Res (Phila) 6:188–195. https://doi.org/10.1158/1940-6207.CAPR-12-0374
doi: 10.1158/1940-6207.CAPR-12-0374
pubmed: 23466816
Garofalo C (2006) Increased expression of leptin and the leptin receptor as a marker of breast cancer progression: possible role of obesity-related stimuli. Clin Cancer Res 12:1447–1453. https://doi.org/10.1158/1078-0432.CCR-05-1913
doi: 10.1158/1078-0432.CCR-05-1913
pubmed: 16533767
Mhaidat NM, Alzoubi KH, Kubas MA et al (2021) High levels of leptin and non-high molecular weight-adiponectin in patients with colorectal cancer: association with chemotherapy and common genetic polymorphisms. Biomed Rep 14:1–1. https://doi.org/10.3892/br.2020.1389
doi: 10.3892/br.2020.1389
Akinci M, Kosova F, Cetin B et al (2009) Leptin levels in thyroid cancer. Asian J Surg 32:216–223. https://doi.org/10.1016/S1015-9584(09)60397-3
doi: 10.1016/S1015-9584(09)60397-3
pubmed: 19892624
Kamel HFM, Nassir AM, Al refai AA, (2020) Assessment of expression levels of leptin and leptin receptor as potential biomarkers for risk of prostate cancer development and aggressiveness. Cancer Med 9:5687–5696. https://doi.org/10.1002/cam4.3082
doi: 10.1002/cam4.3082
pubmed: 32573960
pmcid: 7402836
Arisan ED, Arisan S, Atis G et al (2009) Serum adipocytokine levels in prostate cancer patients. Urol Int 82:203–208. https://doi.org/10.1159/000200801
doi: 10.1159/000200801
pubmed: 19322011
Aref S, Ibrahim L, Azmy E, Al Ashary R (2013) Impact of serum adiponectin and leptin levels in acute leukemia. Hematology 18:198–203. https://doi.org/10.1179/1607845412Y.0000000059
doi: 10.1179/1607845412Y.0000000059
pubmed: 23321463
Yu W, Cao D-D, Li Q-b et al (2016) Adipocytes secreted leptin is a pro-tumor factor for survival of multiple myeloma under chemotherapy. Oncotarget 7:86075–86086. https://doi.org/10.18632/oncotarget.13342
doi: 10.18632/oncotarget.13342
pubmed: 27863383
pmcid: 5349898
Riolfi M, Ferla R, Del Valle L et al (2010) Leptin and its receptor are overexpressed in brain tumors and correlate with the degree of malignancy. Brain Pathol 20:481–489. https://doi.org/10.1111/j.1750-3639.2009.00323.x
doi: 10.1111/j.1750-3639.2009.00323.x
pubmed: 19775291
Zhang L, Yuan Q, Li M et al (2020) The association of leptin and adiponectin with hepatocellular carcinoma risk and prognosis: a combination of traditional, survival, and dose-response meta-analysis. BMC Cancer 20:1167. https://doi.org/10.1186/s12885-020-07651-1
doi: 10.1186/s12885-020-07651-1
pubmed: 33256658
pmcid: 7708253
Wei X, Liu Y, Gong C, et al (2017) Targeting Leptin as a Therapeutic Strategy against Ovarian Cancer Peritoneal Metastasis. In: Anti-Cancer Agents in Medicinal Chemistry. http://www.eurekaselect.com/148597/article . Accessed 30 May 2020
Zhang Y, Liu L, Li C, Ai H (2014) Correlation analysis between the expressions of leptin and its receptor (ObR) and clinicopathology in endometrial cancer. Cancer Biomarkers 14:353–359. https://doi.org/10.3233/CBM-140415
doi: 10.3233/CBM-140415
pubmed: 25171477
Koda M, Sulkowska M, Kanczuga-Koda L et al (2007) Expression of the obesity hormone leptin and its receptor correlates with hypoxia-inducible factor-1α in human colorectal cancer. Ann Oncol 18:vi116–vi119. https://doi.org/10.1093/annonc/mdm238
doi: 10.1093/annonc/mdm238
pubmed: 17591803
Uddin S, Bu R, Ahmed M et al (2009) Overexpression of leptin receptor predicts an unfavorable outcome in Middle Eastern ovarian cancer. Mol Cancer 8:74. https://doi.org/10.1186/1476-4598-8-74
doi: 10.1186/1476-4598-8-74
pubmed: 19765303
pmcid: 2754986
Gorrab A, Pagano A, Ayed K et al (2020) Leptin promotes prostate cancer proliferation and migration by stimulating STAT3 pathway. Nutr Cancer. https://doi.org/10.1080/01635581.2020.1792946
doi: 10.1080/01635581.2020.1792946
pubmed: 32698628
Sultana R, Kataki ACh, Borthakur BB et al (2017) Imbalance in leptin-adiponectin levels and leptin receptor expression as chief contributors to triple negative breast cancer progression in Northeast India. Gene 621:51–58. https://doi.org/10.1016/j.gene.2017.04.021
doi: 10.1016/j.gene.2017.04.021
pubmed: 28414093
Dubois V, Jardé T, Delort L et al (2014) Leptin induces a proliferative response in breast cancer cells but not in normal breast cells. Nutr Cancer 66:645–655. https://doi.org/10.1080/01635581.2014.894104
doi: 10.1080/01635581.2014.894104
pubmed: 24738610
Onuma M, Bub JD, Rummel TL, Iwamoto Y (2003) Prostate cancer cell-adipocyte interaction leptin mediates androgen-independent prostate cancer cell proliferation through c-Jun NH2-terminal kinase. J Biol Chem 278:42660–42667. https://doi.org/10.1074/jbc.M304984200
doi: 10.1074/jbc.M304984200
pubmed: 12902351
Ptak A, Kolaczkowska E, Gregoraszczuk EL (2013) Leptin stimulation of cell cycle and inhibition of apoptosis gene and protein expression in OVCAR-3 ovarian cancer cells. Endocrine 43:394–403. https://doi.org/10.1007/s12020-012-9788-7
doi: 10.1007/s12020-012-9788-7
pubmed: 22968658
Liu Y, Lv L, Xiao W et al (2011) Leptin activates STAT3 and ERK1/2 pathways and induces endometrial cancer cell proliferation. J Huazhong Univ Sci Technol [Med Sci] 31:365–370. https://doi.org/10.1007/s11596-011-0382-7
doi: 10.1007/s11596-011-0382-7
Jardé T, Perrier S, Vasson M-P, Caldefie-Chézet F (2011) Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer 47:33–43. https://doi.org/10.1016/j.ejca.2010.09.005
doi: 10.1016/j.ejca.2010.09.005
pubmed: 20889333
Chen C, Chang Y-C, Liu C-L et al (2007) Leptin induces proliferation and anti-apoptosis in human hepatocarcinoma cells by up-regulating cyclin D1 and down-regulating Bax via a Janus kinase 2-linked pathway. Endocr Relat Cancer 14:513–529. https://doi.org/10.1677/ERC-06-0027
doi: 10.1677/ERC-06-0027
pubmed: 17639064
Chen C, Chang Y-C, Liu C-L et al (2006) Leptin-induced growth of human ZR-75-1 breast cancer cells is associated with up-regulation of cyclin D1 and c-Myc and down-regulation of tumor suppressor p53 and p21WAF1/CIP1. Breast Cancer Res Treat 98:121–132. https://doi.org/10.1007/s10549-005-9139-y
doi: 10.1007/s10549-005-9139-y
pubmed: 16752079
Okumura M, Yamamoto M, Sakuma H et al (2002) Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-α and PPAR expression. Biochimica et Biophys Acta (BBA)—Mol Cell Res 1592:107–116. https://doi.org/10.1016/S0167-4889(02)00276-8
doi: 10.1016/S0167-4889(02)00276-8
Liu L, Wang L, Zheng J, Tang G (2013) Leptin promotes human endometrial carcinoma cell proliferation by enhancing aromatase (P450arom) expression and estradiol formation. Eur J Obstet Gynecol Reprod Biol 170:198–201. https://doi.org/10.1016/j.ejogrb.2013.04.004
doi: 10.1016/j.ejogrb.2013.04.004
pubmed: 23932299
Pham D, Tilija Pun N, Park P (2021) Autophagy activation and SREBP-1 induction contribute to fatty acid metabolic reprogramming by leptin in breast cancer cells. Mol Oncol 15:657–678. https://doi.org/10.1002/1878-0261.12860
doi: 10.1002/1878-0261.12860
pubmed: 33226729
Perera CN, Chin HG, Duru N, Camarillo IG (2008) Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression. J Endocrinol 199:221–233. https://doi.org/10.1677/JOE-08-0215
doi: 10.1677/JOE-08-0215
pubmed: 18715880
Cao H, Huang Y, Wang L et al (2016) Leptin promotes migration and invasion of breast cancer cells by stimulating IL-8 production in M2 macrophages. Oncotarget 7:65441–65453. https://doi.org/10.18632/oncotarget.11761
doi: 10.18632/oncotarget.11761
pubmed: 27588409
pmcid: 5323167
Sharma D, Saxena NK, Vertino PM, Anania FA (2006) Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocr Relat Cancer 13:629–640. https://doi.org/10.1677/erc.1.01169
doi: 10.1677/erc.1.01169
pubmed: 16728588
pmcid: 2925427
Yan D, Avtanski D, Saxena NK, Sharma D (2012) Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways. J Biol Chem 287:8598–8612. https://doi.org/10.1074/jbc.M111.322800
doi: 10.1074/jbc.M111.322800
pubmed: 22270359
pmcid: 3318705
Wei L, Li K, Pang X et al (2016) Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2. J Exp Clin Cancer Res. https://doi.org/10.1186/s13046-016-0446-4
doi: 10.1186/s13046-016-0446-4
pubmed: 27821177
pmcid: 5100324
Lin W, Cuiping T, Kuangfa L, et al (2015) Activation of IL-8 via PI3K/Akt-dependent pathway is involved in leptin-mediated epithelial-mesenchymal transition in human breast cancer cells. https://www.tandfonline.com/doi/full/ https://doi.org/10.1080/15384047.2015.1056409 . Accessed 30 Jul 2020
Xu M, Cao F-L, Li N et al (2018) Leptin induces epithelial-to-mesenchymal transition via activation of the ERK signaling pathway in lung cancer cells. Oncol Lett 16:4782. https://doi.org/10.3892/ol.2018.9230
doi: 10.3892/ol.2018.9230
pubmed: 30250542
pmcid: 6144616
Duan L, Lu Y, Xie W et al (2020) Leptin promotes bone metastasis of breast cancer by activating the SDF-1/CXCR4 axis. Aging (Albany NY) 12:16172–16182. https://doi.org/10.18632/aging.103599
doi: 10.18632/aging.103599
pubmed: 32836215
Hoffmann M, Fiedor E, Ptak A (2016) 17β-estradiol reverses leptin-inducing ovarian cancer cell migration by the PI3K/Akt signaling pathway. Reprod Sci 23:1600–1608. https://doi.org/10.1177/1933719116648214
doi: 10.1177/1933719116648214
pubmed: 27255147
Sobrinho Santos EM, Guimarães TA, Santos HO et al (2017) Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma. Tumour Biol 39:1010428317699130. https://doi.org/10.1177/1010428317699130
doi: 10.1177/1010428317699130
pubmed: 28459203
Ghasemi A, Hashemy SI, Aghaei M, Panjehpour M (2018) Leptin induces matrix metalloproteinase 7 expression to promote ovarian cancer cell invasion by activating ERK and JNK pathways. J Cell Biochem 119:2333–2344. https://doi.org/10.1002/jcb.26396
doi: 10.1002/jcb.26396
pubmed: 28885729
Lin M-C, Tsai S-Y, Wang F-Y et al (2013) Leptin induces cell invasion and the upregulation of matrilysin in human colon cancer cells. Biomedicine 3:174–180. https://doi.org/10.1016/j.biomed.2013.09.001
doi: 10.1016/j.biomed.2013.09.001
Fan Y, Gan Y, Shen Y et al (2015) Leptin signaling enhances cell invasion and promotes the metastasis of human pancreatic cancer via increasing MMP-13 production. Oncotarget. https://doi.org/10.18632/oncotarget.3878
doi: 10.18632/oncotarget.3878
pubmed: 26675761
pmcid: 4868718
Yeh W-L, Lu D-Y, Lee M-J, Fu W-M (2009) Leptin induces migration and invasion of glioma cells through MMP-13 production. Glia 57:454–464. https://doi.org/10.1002/glia.20773
doi: 10.1002/glia.20773
pubmed: 18814267
Dong Z, Xu X, Du L et al (2013) Leptin-mediated regulation of MT1-MMP localization is KIF1B dependent and enhances gastric cancer cell invasion. Carcinogenesis 34:974–983. https://doi.org/10.1093/carcin/bgt028
doi: 10.1093/carcin/bgt028
pubmed: 23354307
Ghasemi A, Hashemy SI, Aghaei M, Panjehpour M (2017) RhoA/ROCK pathway mediates leptin-induced uPA expression to promote cell invasion in ovarian cancer cells. Cell Signal 32:104–114. https://doi.org/10.1016/j.cellsig.2017.01.020
doi: 10.1016/j.cellsig.2017.01.020
pubmed: 28104444
Bao B, Ahmad A, Azmi AS et al (2013) Overview of cancer stem cells (CSCs) and mechanisms of their regulation: implications for cancer therapy. Curr Protoc Pharmacol. https://doi.org/10.1002/0471141755.ph1425s61
doi: 10.1002/0471141755.ph1425s61
pubmed: 23744710
pmcid: 3733496
Zheng Q, Dunlap SM, Zhu J et al (2011) Leptin deficiency suppresses MMTV-Wnt-1 mammary tumor growth in obese mice and abrogates tumor initiating cell survival. Endocr Relat Cancer 18:491–503. https://doi.org/10.1530/ERC-11-0102
doi: 10.1530/ERC-11-0102
pubmed: 21636700
pmcid: 3197719
Giordano C, Chemi F, Panza S et al (2015) Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity. Oncotarget 7:1262–1275
doi: 10.18632/oncotarget.6014
pmcid: 4811458
Chang C-C, Wu M-J, Yang J-Y et al (2015) Leptin–STAT3–G9a signaling promotes obesity-mediated breast cancer progression. Cancer Res 75:2375–2386. https://doi.org/10.1158/0008-5472.CAN-14-3076
doi: 10.1158/0008-5472.CAN-14-3076
pubmed: 25840984
pmcid: 4694051
Zuazo-Gaztelu I, Casanovas O (2018) Unraveling the role of angiogenesis in cancer ecosystems. Front Oncol. https://doi.org/10.3389/fonc.2018.00248
doi: 10.3389/fonc.2018.00248
pubmed: 30013950
pmcid: 6036108
Cao Y (2013) Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity. Cell Metab 18:478–489. https://doi.org/10.1016/j.cmet.2013.08.008
doi: 10.1016/j.cmet.2013.08.008
pubmed: 24035587
Garonna E, Botham KM, Birdsey GM et al (2011) Vascular endothelial growth factor receptor-2 couples cyclo-oxygenase-2 with pro-angiogenic actions of leptin on human endothelial cells. PloS one 6:e18823. https://doi.org/10.1371/journal.pone.0018823
doi: 10.1371/journal.pone.0018823
pubmed: 21533119
pmcid: 3078934
Gonzalez RR, Cherfils S, Escobar M et al (2006) Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2). J Biol Chem 281:26320–26328. https://doi.org/10.1074/jbc.M601991200
doi: 10.1074/jbc.M601991200
pubmed: 16825198
Gonzalez-Perez RR, Xu Y, Guo S et al (2010) Leptin upregulates VEGF in breast cancer via canonic and non-canonical signalling pathways and NFκB/HIF-1α activation. Cell Signal 22:1350–1362. https://doi.org/10.1016/j.cellsig.2010.05.003
doi: 10.1016/j.cellsig.2010.05.003
pubmed: 20466060
pmcid: 2928711
Gonzalez-Perez R, Lanier V, Newman G (2013) Leptin’s pro-angiogenic signature in breast cancer. Cancers 5:1140–1162. https://doi.org/10.3390/cancers5031140
doi: 10.3390/cancers5031140
pubmed: 24202338
pmcid: 3795383
Guo S, Gonzalez-Perez RR (2011) Notch, IL-1 and leptin crosstalk outcome (NILCO) is critical for leptin-induced proliferation, migration and VEGF/VEGFR-2 expression in breast cancer. PloS one 6:e21467. https://doi.org/10.1371/journal.pone.0021467
doi: 10.1371/journal.pone.0021467
pubmed: 21731759
pmcid: 3121792
Michelet X, Dyck L, Hogan A et al (2018) Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol 19:1330–1340. https://doi.org/10.1038/s41590-018-0251-7
doi: 10.1038/s41590-018-0251-7
pubmed: 30420624
Cava AL, Matarese G (2004) The weight of leptin in immunity. Nat Rev Immunol 4:371–379. https://doi.org/10.1038/nri1350
doi: 10.1038/nri1350
pubmed: 15122202
Lamas B, Goncalves-Mendes N, Nachat-Kappes R et al (2013) Leptin modulates dose-dependently the metabolic and cytolytic activities of NK-92 cells. J Cell Physiol 228:1202–1209. https://doi.org/10.1002/jcp.24273
doi: 10.1002/jcp.24273
pubmed: 23129404
Bähr I, Goritz V, Doberstein H, et al (2017) Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence. Journal of Nutrition and Metabolism. https://www.hindawi.com/journals/jnme/2017/4297025/ . Accessed 21 Apr 2020
Wrann CD, Laue T, Hübner L et al (2011) Short-term and long-term leptin exposure differentially affect human natural killer cell immune functions. Am J Physiol-Endocrinol Metab 302:E108–E116. https://doi.org/10.1152/ajpendo.00057.2011
doi: 10.1152/ajpendo.00057.2011
pubmed: 21952038
Yang H, Youm Y-H, Vandanmagsar B et al (2009) Obesity accelerates thymic aging. Blood 114:3803–3812. https://doi.org/10.1182/blood-2009-03-213595
doi: 10.1182/blood-2009-03-213595
pubmed: 19721009
pmcid: 2773495
Wang Z, Aguilar EG, Luna JI et al (2019) Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med 25:141–151. https://doi.org/10.1038/s41591-018-0221-5
doi: 10.1038/s41591-018-0221-5
pubmed: 30420753
Kado T, Nawaz A, Takikawa A et al (2019) Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis. Sci Rep 9:12284. https://doi.org/10.1038/s41598-019-48678-0
doi: 10.1038/s41598-019-48678-0
pubmed: 31439906
pmcid: 6706391
Zhang C, Yue C, Herrmann A et al (2020) STAT3 activation-induced fatty acid oxidation in CD8+ T effector cells is critical for obesity-promoted breast tumor growth. Cell Metab 31:148-161.e5. https://doi.org/10.1016/j.cmet.2019.10.013
doi: 10.1016/j.cmet.2019.10.013
pubmed: 31761565
Pyzer AR, Cole L, Rosenblatt J, Avigan DE (2016) Myeloid-derived suppressor cells as effectors of immune suppression in cancer: MDSC mediate immune suppression in cancer. Int J Cancer 139:1915–1926. https://doi.org/10.1002/ijc.30232
doi: 10.1002/ijc.30232
pubmed: 27299510
Bao Y, Mo J, Ruan L, Li G (2015) Increased monocytic CD14+HLADRlow/−myeloid-derived suppressor cells in obesity. Mol Med Rep 11:2322–2328. https://doi.org/10.3892/mmr.2014.2927
doi: 10.3892/mmr.2014.2927
pubmed: 25384365
Clements VK, Long T, Long R et al (2018) Frontline science: high fat diet and leptin promote tumor progression by inducing myeloid-derived suppressor cells. J Leukoc Biol 103:395–407. https://doi.org/10.1002/JLB.4HI0517-210R
doi: 10.1002/JLB.4HI0517-210R
pubmed: 29345342
Nishikawa H, Sakaguchi S (2010) Regulatory T cells in tumor immunity. Int J Cancer 127:759–767. https://doi.org/10.1002/ijc.25429
doi: 10.1002/ijc.25429
pubmed: 20518016
Wagner N-M, Brandhorst G, Czepluch F et al (2013) Circulating regulatory T cells are reduced in obesity and may identify subjects at increased metabolic and cardiovascular risk. Obesity 21:461–468. https://doi.org/10.1002/oby.20087
doi: 10.1002/oby.20087
pubmed: 23592653
De Rosa V, Procaccini C, Calì G et al (2007) A key role of leptin in the control of regulatory T cell proliferation. Immunity 26:241–255. https://doi.org/10.1016/j.immuni.2007.01.011
doi: 10.1016/j.immuni.2007.01.011
pubmed: 17307705
Karabulut S, Usul Afsar C, Karabulut M, et al (2016) Serum leptin levels may have diagnostic and predictive roles in patients with pancreatic adenocarcinoma treated with gemcitabine-based chemotherapy. J BUON 21:895–902
Bain GH, Collie-Duguid E, Murray GI et al (2014) Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas. Br J Cancer 110:1525–1534. https://doi.org/10.1038/bjc.2014.45
doi: 10.1038/bjc.2014.45
pubmed: 24569475
pmcid: 3960617
Harbuzariu A, Gonzalez-Perez RR (2018) Leptin-Notch axis impairs 5-fluorouracil effects on pancreatic cancer. Oncotarget 9:18239–18253. https://doi.org/10.18632/oncotarget.24435
doi: 10.18632/oncotarget.24435
pubmed: 29719602
pmcid: 5915069
Shen L, Luo H-S, Sun J, Zhao L (2011) Leptin decreases the sensitivity of human colon cancer cell HT-29 to 5-flurouracil. African Journal of Pharmacy and Pharmacology 5
Nadal-Serrano M, Sastre-Serra J, Valle A et al (2015) Chronic-leptin attenuates cisplatin cytotoxicity in MCF-7 breast cancer cell line. CPB 36:221–232. https://doi.org/10.1159/000374066
doi: 10.1159/000374066
Gu F, Zhang H, Yao L et al (2019) Leptin contributes to the taxol chemoresistance in epithelial ovarian cancer. Oncol Lett 18:561–570. https://doi.org/10.3892/ol.2019.10381
doi: 10.3892/ol.2019.10381
pubmed: 31289528
pmcid: 6546982
Efferth T, Fabry U, Osieka R (2000) Leptin contributes to the protection of human leukemic cells from cisplatinum cytoxicity. Anticancer Res 20:2541–2546
pubmed: 10953324
Wang F, Zhang L, Sai B et al (2019) BMSC-derived leptin and IGFBP2 promote erlotinib resistance in lung adenocarcinoma cells through IGF-1R activation in hypoxic environment. Cancer Biol Ther 21:61–71. https://doi.org/10.1080/15384047.2019.1665952
doi: 10.1080/15384047.2019.1665952
pubmed: 31559898
pmcid: 7012080
da Rocha RG, Santos EMS, Santos EM et al (2019) Leptin impairs the therapeutic effect of ionizing radiation in oral squamous cell carcinoma cells. J Oral Pathol Med 48:17–23. https://doi.org/10.1111/jop.12786
doi: 10.1111/jop.12786
pubmed: 30290014
Naik A, Monjazeb AM, Decock J (2019) The obesity paradox in cancer, tumor immunology, and immunotherapy: potential therapeutic implications in triple negative breast cancer. Front Immunol. https://doi.org/10.3389/fimmu.2019.01940
doi: 10.3389/fimmu.2019.01940
pubmed: 31475003
pmcid: 6703078
Murphy KA, James BR, Sjaastad FV et al (2018) Cutting edge: elevated leptin during diet-induced obesity reduces the efficacy of tumor immunotherapy. J Immunol 201:1837–1841. https://doi.org/10.4049/jimmunol.1701738
doi: 10.4049/jimmunol.1701738
pubmed: 30135180
Gertler A, Solomon G (2013) Leptin-activity blockers: development and potential use in experimental biology and medicine. Can J Physiol Pharmacol 91:873–882. https://doi.org/10.1139/cjpp-2013-0012
doi: 10.1139/cjpp-2013-0012
pubmed: 24117254
Catalano S, Leggio A, Barone I et al (2015) A novel leptin antagonist peptide inhibits breast cancer growth in vitro and in vivo. J Cell Mol Med 19:1122–1132. https://doi.org/10.1111/jcmm.12517
doi: 10.1111/jcmm.12517
pubmed: 25721149
pmcid: 4420614
Panza S, Gelsomino L, Malivindi R et al (2019) Leptin receptor as a potential target to inhibit human testicular seminoma growth. Am J Pathol 189:687–698. https://doi.org/10.1016/j.ajpath.2018.11.012
doi: 10.1016/j.ajpath.2018.11.012
pubmed: 30610844
Otvos L, Kovalszky I, Riolfi M et al (2011) Efficacy of a leptin receptor antagonist peptide in a mouse model of triple-negative breast cancer. Eur J Cancer 47:1578–1584. https://doi.org/10.1016/j.ejca.2011.01.018
doi: 10.1016/j.ejca.2011.01.018
pubmed: 21353530
Napoleone E, Cutrone A, Cugino D et al (2012) Leptin upregulates tissue factor expression in human breast cancer MCF-7 cells. Thromb Res 129:641–647. https://doi.org/10.1016/j.thromres.2011.07.037
doi: 10.1016/j.thromres.2011.07.037
pubmed: 21840575
Fusco R, Galgani M, Procaccini C et al (2010) Cellular and molecular crosstalk between leptin receptor and estrogen receptor-α in breast cancer: molecular basis for a novel therapeutic setting. Endocr Relat Cancer 17:373–382. https://doi.org/10.1677/ERC-09-0340
doi: 10.1677/ERC-09-0340
pubmed: 20410173
Iversen PO, Drevon CA, Reseland JE (2002) Prevention of leptin binding to its receptor suppresses rat leukemic cell growth by inhibiting angiogenesis. Blood 100:4123–4128. https://doi.org/10.1182/blood-2001-11-0134
doi: 10.1182/blood-2001-11-0134
pubmed: 12393625
McMurphy T, Xiao R, Magee D et al (2014) The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma. PloS one 9:e89895. https://doi.org/10.1371/journal.pone.0089895
doi: 10.1371/journal.pone.0089895
pubmed: 24587106
pmcid: 3938505
Avtanski DB, Nagalingam A, Kuppusamy P et al (2015) Honokiol abrogates leptin-induced tumor progression by inhibiting Wnt1-MTA1-β-catenin signaling axis in a microRNA-34a dependent manner. Oncotarget 6:16396–16410
doi: 10.18632/oncotarget.3844
pubmed: 26036628
pmcid: 4599277
Benatti FB, Junior AHL (2007) Leptin and endurance exercise: implications of adiposity and insulin. Rev Bras Med Esporte 13:6
Amani Shalamzari S, Daneshfar A, Hassanzadeh Sablouei M, et al (2018) The Effect of Aerobic Training on Tumor Growth, Adiponectin, Leptin and Ghrelin in Mice Models of Breast Cancer. Iranian Red Crescent Medical Journal. http://sites.kowsarpub.com/articles/13305.html . Accessed 30 May 2020