Clinicopathological implications of leptin and leptin receptor expression in papillary thyroid cancer

Zhang, Guo An; Hou, Sen; Han, Shuang; Zhou, Juxiang; Wang, Xu; Cui, Wen

doi:10.3892/ol.2013.1125

Cited by 24 publications

(17 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, no significant correlation was found between OB-R expression levels and BMI values, the presence of lymph node metastases, or patient outcome (data not shown). These results confirm those of Zhang et al, which were obtained with a larger series of patients [25]. In addition, we did not find significant differences between OB-R mRNA and protein levels in the subgroup of PTC tumors carrying the BRAF V600E mutation, proposed as a hallmark of tumor aggressiveness [26, 27], and PTCs with wild-type BRAF .…”

Section: Discussionsupporting

confidence: 92%

Expression of Leptin Receptor and Effects of Leptin on Papillary Thyroid Carcinoma Cells

Celano

Maggisano

Lepore

et al. 2019

International Journal of Endocrinology

View full text Add to dashboard Cite

Background. Obesity has been hypothesized to contribute to the aggressiveness of thyroid cancer through the production of abnormal levels of serum adipokines. Leptin receptor (OB-R) expression has also been documented in papillary thyroid cancer (PTC). Aim. In this translational study, we analyzed in vitro the effects of leptin on the growth and migration of thyroid cancer cells (TPC-1 and K1), the molecular mechanisms underlying leptin’s action, and the influence of prolonged leptin exposure on cell response to a protein kinase inhibitor lenvatinib. The expression levels of OB-R mRNA and protein were also investigated in vivo in a series of aggressive PTCs divided into two groups based on the presence of the BRAF mutation. Results. In TPC-1 and K1 cells, prolonged treatment with leptin (500 ng/ml for 96 h) resulted in a mild increase in the proliferation (about 20% over control only in K1 cells, p<0.05) and in the migration of both cancer cell lines. Immunoblot analysis revealed a slight increase in the phosphorylation of AKT, but no effect on β-catenin and phospho-ERK expressions. The inhibitory effects of lenvatinib on the viability of both cell lines were not influenced by the leptin treatment. OB-R transcript (in fresh tissues) and proteins (in formalin-fixed and paraffin-embedded specimens) were expressed in all PTC tissues examined, with no significant differences between BRAF-mutated and BRAF-wild-type tumors. Conclusions. These results demonstrate leptin’s role in mildly increasing the aggressive phenotype of PTC cells but without influencing the action of lenvatinib. Further studies will clarify whether it is possible to target OB-R, expressed in all aggressive PTCs, as an adjuvant treatment approach for these malignancies.

show abstract

Section: Discussionsupporting

confidence: 92%

Expression of Leptin Receptor and Effects of Leptin on Papillary Thyroid Carcinoma Cells

Celano

Maggisano

Lepore

et al. 2019

International Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…In a Chinese single‐cohort study (BEL 3, GR C) of patients with PTC ( n = 76), leptin and Ob‐R were expressed in 72 and 74% of primary lesions, respectively. The expression of either was associated with greater tumour size but not multifocality or lymph node metastasis . In summary, no conclusive evidence exists on any potential role of leptin in thyroid carcinogenesis.…”

Section: Obesity and Thyroid Cancer Risk: Potential Mediatorsmentioning

confidence: 90%

Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms

2013

View full text Add to dashboard Cite

The incidence of thyroid cancer has been rising over the past few decades along with a parallel increase in obesity. Observational studies have provided evidence for a potential association between the two. By contrast, clinical data for a link between type 2 diabetes mellitus, a condition strongly associated with obesity, and thyroid cancer are limited and largely not supportive of such an association. Obesity leads to hypoadiponectinemia, a pro-inflammatory state, and insulin resistance, which, in turn, leads to high circulating insulin and insulin-like growth factor-1 levels, thereby possibly increasing the risk for thyroid cancer. Thus, insulin resistance possibly plays a pivotal role in underlying the observed association between obesity and thyroid cancer, potentially leading to the development and/or progression of thyroid cancer, through its interconnections with other factors including insulin-like growth factor-1, adipocytokines/cytokines and thyroid-stimulating hormone. In this review, epidemiological and clinical evidence and potential mechanisms underlying the proposed association between obesity and thyroid cancer risk are reviewed. If the association between obesity and thyroid cancer demonstrated in observational studies proves to be causal, targeting obesity (and/or downstream mediators of risk) could be of importance in the prevention and management of thyroid cancer.

show abstract

“…On the other hand, both leptin and Ob-R levels were strongly associated with larger tumor size, nodal metastasis and advanced stage in papillary thyroid carcinoma [125]. Several studies on patients with papillary thyroid cancer documented that expression of leptin and/or Ob-R was directly linked with disease aggressiveness including increased tumor size and lymph node metastasis [126–128]. In addition, it has been found that Ob-R overexpression was significantly associated with the overexpression of anti-apoptotic XIAP and Bcl-X L proteins as well as with poor disease-free survival in cases with papillary thyroid cancer [128].…”

Section: Tumors Of Endocrine and Associated Organsmentioning

confidence: 99%

The potential role of leptin in tumor invasion and metastasis

Ray

Cleary

2017

Cytokine & Growth Factor Reviews

109

View full text Add to dashboard Cite

The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals, elevated leptin levels act as a pro-inflammatory adipokine and are associated with certain types of cancers. Further, a growing body of evidence suggests that higher circulating leptin concentrations and/or elevated expression of leptin receptors (Ob-R) in tumors may be poor prognostic factors. Although the underlying pathological mechanisms of leptin’s association with poor prognosis are not clear, leptin can impact the tumor microenvironment in several ways. For example, leptin is associated with a number of biological components that could lead to tumor cell invasion and distant metastasis. This includes interactions with carcinoma-associated fibroblasts, tumor promoting effects of infiltrating macrophages, activation of matrix metalloproteinases, transforming growth factor-β signaling, etc. Recent studies also have shown that leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for cancer cell migration and/or metastasis. Furthermore, leptin’s potentiating effects on insulin-like growth factor-I, epidermal growth factor receptor and HER2/neu have been reported. Regarding unfavorable prognosis, leptin has been shown to influence both adenocarcinomas and squamous cell carcinomas. Features of poor prognosis such as tumor invasion, lymph node involvement and distant metastasis have been recorded in several cancer types with higher levels of leptin and/or Ob-R. This review will describe the current scenario in a precise manner. In general, obesity indicates poor prognosis in cancer patients.

show abstract

Clinicopathological implications of leptin and leptin receptor expression in papillary thyroid cancer

Cited by 24 publications

References 31 publications

Expression of Leptin Receptor and Effects of Leptin on Papillary Thyroid Carcinoma Cells

Expression of Leptin Receptor and Effects of Leptin on Papillary Thyroid Carcinoma Cells

Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms

The potential role of leptin in tumor invasion and metastasis

Contact Info

Product

Resources

About