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

Abstract

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.

Adiponectin and leptin exert antagonizing effects on proliferation and motility of papillary thyroid cancer cell lines

“…In line with our results, more recently, Celano and colleagues reported that leptin slightly increased cell proliferation of K1 cells but only at the dose of 500 ng/ml at 96 h-time point and increased cell motility [ 8 ]. While, consistent with our result, lower doses of leptin (125 ng/ml) does not impair proliferation in K1 cells.…”

Obesity and Thyroid Cancer Risk: An Update

“…In 2019, Celano and colleagues conducted a translational study to analyze in vitro the molecular mechanisms by which leptin may affect the growth and migration of PTC cell lines. They demonstrated that leptin slightly increased the aggressive phenotype of PTC cells by stimulating proliferation and migration of both TPC and K1 cells [74]. Similar results were obtained by Nigro et al [75] in both BCPAP and K1 cell lines.…”

“…Celano et al also evaluated the effects of leptin exposure on cells in response to lenvatinib, a protein kinase inhibitor. In these experiments, leptin was not able to affect the effect of lenvatinib [74]. The same study also reported that OB-R transcript and proteins were expressed in all PTC tissues examined, with no significant differences between tumors with the BRAF V600E mutation and BRAF wild-type tumors [74].…”

Actions of L-thyroxine (T4) and Tetraiodothyroacetic Acid (Tetrac) on Gene Expression in Thyroid Cancer Cells

“…In the clinical setting of overweight, adipose tissue is expected to secrete leptin protein [27,28]. An endogenous anti-appetite factor, leptin has also been shown to support the growth of certain tumors, including papillary thyroid carcinoma, that express the leptin receptor [4]. There are a variety of other observations that link leptin and thyroid hormone together at cancer cells.…”

“…The clinical behavior of thyroid gland cancers is seen to reflect gene mutation and/or epigenetic changes [1,2], and effects of circulating or local trophic factors [3,4]. Circulating trophic factors include target tissue-specific thyrotropin (TSH) secreted by the pituitary gland and adipose tissue-source leptin, which enhances growth of a variety of tumors, including those of the thyroid gland [5].…”