Clinicopathologic significance of leptin and leptin receptor expressions in papillary thyroid carcinoma

Cheng, Shih‐Ping; Chi, Chin‐Wen; Tzen, Chin‐Yuan; Yang, Tsen-Long; Lee, Jie-Jen; Liu, Tsang-Pai; Liu, Chien‐Liang

doi:10.1016/j.surg.2009.11.004

Cited by 73 publications

(54 citation statements)

References 39 publications

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“…Frequency of leptin expression dramatically increases from normal colonic mucosa to adenomas and adenocarcinomas along with neoplastic progression (25). Previously we have shown that leptin and leptin receptor are co-expressed in thyroid cancer tissues and cancer cells (21,23), suggesting the possibility of autocrine/paracrine regulation. In obesity, adipose tissue hypoxia is an important factor in the development of inflammatory response, increased leptin and reduced adiponectin gene expressions (26).…”

Section: Discussionmentioning

confidence: 93%

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Leptin enhances migration of human papillary thyroid cancer cells through the PI3K/AKT and MEK/ERK signaling pathways

Cheng

Yin

Hsu³

et al. 2011

Oncol Rep

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Abstract. The incidence of thyroid cancer has remarkably increased in recent years. Epidemiologic data suggest that obesity is associated with an increased incidence of several types of malignancies, including thyroid cancer. Leptin, an adipocyte-derived cytokine, has been shown to be involved in cancer development and progression. We previously demonstrated that papillary thyroid cancer expressing leptin receptor and/or leptin has a higher incidence of lymph node metastasis. In this study, we investigated the effects of leptin on cell migration in K1 and B-CPAP papillary thyroid cancer cells. Expression of leptin receptor was observed in both cell lines. Leptin enhanced the migratory activity significantly in a dose-dependent manner. We showed that leptin induced AKT and extracellular signal-regulated kinase (ERK) phosphorylation. Inhibition of phosphatidylinositol 3-kinase and ERK activation using pharmacological inhibitors effectively blocked leptin-induced migration of K1 and B-CPAP cells. Taken together, this study provides new mechanistic evidence for a role of leptin in the regulation of papillary thyroid cancer progression by stimulating tumor cell migration.

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Section: Discussionmentioning

confidence: 93%

“…Using immunohistochemical analysis, we and others have reported that leptin and leptin receptor were overexpressed in papillary thyroid cancer and metastatic lymph nodes (21,22). Expression of leptin receptor and/or leptin in primary tumors was associated with higher incidence of lymph node metastasis.…”

Section: Introductionmentioning

confidence: 83%

Leptin enhances migration of human papillary thyroid cancer cells through the PI3K/AKT and MEK/ERK signaling pathways

Cheng

Yin

Hsu³

et al. 2011

Oncol Rep

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“…Moreover, elevated expression of leptin and/or leptin receptor in papillary thyroid cancer is associated with neoplasm aggressiveness, including tumor size and lymph node metastasis (Cheng et al 2010). Recently, Lee et al showed the presence of an expanded intrathyroidal adipose depot and steatosis in thyroid epithelial cells in obese patients (Lee et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model

Park

Han

Zhao

et al. 2015

Endocrine-Related Cancer

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Compelling epidemiologic studies indicate that obesity is a risk factor for many human cancers, including thyroid cancer. In recent decades, the incidence of thyroid cancer has dramatically increased along with a marked rise in obesity prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the obese phenotype in a mouse model of thyroid cancer (Thrb PV/PV Pten C/K mice). Moreover, HFD activates the STAT3 signal pathway to promote more aggressive tumor phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of STAT3 activity, on HFD-induced aggressive cancer progression in the mouse model of thyroid cancer. WT and Thrb PV/PV Pten C/K mice were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of S3I-201 on HFD-induced thyroid cancer progression, the leptin-JAK2-STAT3 signaling pathway, and key regulators of epithelial-mesenchymal transition (EMT). S3I-201 effectively inhibited HFD-induced aberrant activation of STAT3 and its downstream targets to markedly inhibit thyroid tumor growth and to prolong survival. Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase 4 (CDK4), CDK6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated Thrb PV/PV Pten C/K mice. Reduced occurrence of vascular invasion and blocking of anaplasia and lung metastasis in thyroid tumors of S3I-201-treated Thrb PV/PV Pten C/K mice were mediated via decreased expression of vimentin and matrix metalloproteinases, two key effectors of EMT. The present findings suggest that inhibition of the STAT3 activity would be a novel treatment strategy for obesity-induced thyroid cancer.

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“…Thus, leptin interacts with several factors that participate in diverse carcinogenic stages, and its relationship with breast, prostate, colorectal, hepatocellular, pancreatic, and lung cancers, as well as thyroid cancer, has consistently been demonstrated in the literature (Dutta et al 2012, Vansaun 2013. Concerning thyroid cancers, and more specifically DTCs, leptin and OBR (LEPR) expression were first demonstrated by Cheng et al (2010b), who found them associated with a high risk of lymph node metastases. Other groups have also reported the involvement of leptin in the clinical phenotype of DTCs, and it has been suggested that leptin may affect the migration of thyroid cells, collaborating for a worse prognosis and metastasis formation (Cheng et al 2010a, Kim et al 2013b.…”

Section: Inflammationmentioning

confidence: 95%

Obesity and thyroid cancer

Marcello,

Cunha,

Batista

et al. 2014

Endocrine Related Cancer

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Many studies have provided observational data on the association of obesity and thyroid cancers, but only few of them propose mechanisms that would permit a better understanding of the causal molecular mechanisms of this association. Considering that there is an increasing incidence of both obesity and thyroid cancers, we need to summarize and link recent studies in order to characterize and understand the contribution of obesity-related factors that might affect thyroid cancer development and progression. Adipose tissue is involved in many vital processes, including insulin sensitivity, angiogenesis, regulation of energy balance, activation of the complement system, and responses such as inflammation. Although these processes have their own molecular pathways, they involve the same molecules through which obesity and adipose tissue might exert their roles in carcinogenesis, not only affecting MAPK and PI3K or even insulin pathways, but also recruiting local inflammatory responses that could result in disease formation and progression. This review describes five important issues that might explain the link between excessive weight and thyroid cancer: thyroid hormones, insulin resistance, adipokines, inflammation, and sexual hormones.

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Clinicopathologic significance of leptin and leptin receptor expressions in papillary thyroid carcinoma

Cited by 73 publications

References 39 publications

Leptin enhances migration of human papillary thyroid cancer cells through the PI3K/AKT and MEK/ERK signaling pathways

Leptin enhances migration of human papillary thyroid cancer cells through the PI3K/AKT and MEK/ERK signaling pathways

Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model

Obesity and thyroid cancer

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