scholarly journals MON-532 Characterization of the Angiogenic Factor SFRP2 in Papillary Thyroid Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Wyatt O Wofford ◽  
Rupak Mukherjee ◽  
Julie Siegel ◽  
Denise Garcia ◽  
Eleanor Hilliard ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Thyroid Tissue ◽  
Angiogenic Factor ◽  
Papillary Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Treatment Groups ◽  
Vehicle Treatment

Abstract Over the last decade, there has been an average annual increase of 3.1% in thyroid cancer diagnosis in the U.S. Papillary thyroid carcinoma (PTC) accounts for 80% of all thyroid cancer diagnoses. However, few molecular markers exist to identify clinically aggressive phenotypes. The angiogenic factor, secreted frizzled-related protein 2 (SFRP2), is associated with a poor prognosis in several malignancies including breast cancer and melanoma. The role of SFRP2 in PTC has yet to be investigated. The aims of this study were to determine the differential expression of SFRP2 in PTC, benign thyroid adenomas, normal thyroid tissue (from patients without cancer), and normal adjacent tissue (NAT) (non-cancerous tissue from patients with PTC) and investigate the role of SFRP2 in tumor development in two PTC cell lines, PTC classical variant (PTC-CV) and PTC follicular variant (PTC-FV), upon treatment with a humanized anti-SFRP2 monoclonal antibody (hSFRP2 mAb). Immunohistochemistry (IHC) was performed using human tissue protein microarrays including 226 PTC, 79 benign adenomas, 112 NAT, and 30 normal thyroid tissue samples. In-vitro proliferation and apoptosis experiments were performed on MDA-T41 (PTC-CV) and MDA-T68 (PTC-FV) cell lines by treating with hSFRP2 mAb, Xolair IgG control, and a vehicle control. SFRP2 expression was significantly higher in PTC compared with benign adenomas and normal thyroid (mean expression scores 9, 6, and 1, respectively; p<0.05). SFRP2 expression was significantly higher in NAT than normal thyroid (mean expression score 4 and 0, respectively, p<0.05). Apoptotic rates were increased by 40% and 62% in the PTC-CV hSFRP2 mAb treatment group compared with the Xolair and vehicle treatment groups, respectively (p<0.05). Apoptotic rates were increased by 126% and 59% in the PTC-FV hSFRP2 mAb treatment group compared with the Xolair and vehicle treatment groups, respectively (p<0.05). Treatment with hSFRP2 mAb had no significant effect on proliferation in either cell line. In conclusion, SFRP2 expression is significantly higher in PTC than in benign adenomas and normal thyroid tissue. SFRP2 expression in NAT is significantly higher than in normal thyroid tissue and not significantly different from benign adenomas. SFRP2 expression in nonmalignant tissue adjacent to PTC could be due to expression in the tumor microenvironment. Treatment with a novel hSFPR2 mAb increases apoptotic rates in two different PTC cell lines. These data suggest that SFPR2 is involved in tumorigenesis of PTC.

scholarly journals EZH2 upregulation by ERα induces proliferation and migration of papillary thyroid carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Liqiong Xue ◽  
Hongzhu Yan ◽  
Ying Chen ◽  
Qifa Zhang ◽  
Xin Xie ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Cell Lines ◽  
Thyroid Tissue ◽  
Papillary Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Realtime Pcr ◽  
Ezh2 Expression ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide in recent years. Therefore, novel potential therapeutic targets for PTC are urgently needed. Enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to PRC2, plays important roles in epigenetic silencing and cell cycle regulation. EZH2 overexpression has been found in several malignant tumor tissues, while its expression and function in PTC are largely unknown. Methods Sixty-five cases of PTC tissue confirmed by pathology and 30 cases of normal thyroid tissue adjacent to PTC tissue were collected from patients undergoing surgical treatment, between February 2003 and February 2006. We investigated the clinic pathologic significance of EZH2 expression using Realtime-PCR and IHC in 65 human PTC tissues and 30 normal thyroid tissue samples. The EZH2 expression in human PTC cell lines (K1 and W3) and the normal thyroid follicular epithelial cell line Nthy-ori 3–1 was analyzed by Western blotting and Realtime PCR. The expressions of ERα and ERβ in cell lines were analyzed by Realtime PCR.The tumor cell biological behavior was evaluated by CCK8 assay, colony formation assay, transwell migration assay and xenograft tumors model. Results Higher rate of EZH2 expression was found in PTC tissues than in normal thyroid tissues, EZH2 expression is associated with lymph node metastasis and recurrent. Inhibition of EZH2 in PTC cell lines downregulates cellular proliferation and migration. PTC is a disease with high incidence of female and E2-ERα upregulates EZH2 expression. Conclusions These results suggest a potential role of EZH2 for the PTC growth and metastasis. As a novel therapy, a pharmacological therapy targeting EZH2 has full potential in treatment of PTC.

scholarly journals Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Bo Gao ◽  
Lingji Guo ◽  
Donglin Luo ◽  
Yan Jiang ◽  
Jianjie Zhao ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Tissue ◽  
Lymphatic Vessels ◽  
Steroid Receptor ◽  
Human Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Steroid Receptor Coactivator ◽  
Lymphatic Metastases ◽  
Factor C

Thyroid cancer is the most common endocrine cancer, and has a high incidence of lymphatic metastasis. Vascular endothelial growth factor C (VEGFC) is essential for development of lymphatic vessels and lymphatic metastases during carcinogenesis. Steroid receptor coactivator-1 (SRC-1) interacts with nuclear receptors and transcription factors to promote tumor proliferation and metastasis. However, the correlation between SRC-1 and VEGFC levels in the lymphatic metastases of thyroid cancer remains unclear. We analyzed 20-paired specimens of thyroid cancer tissue and normal thyroid tissue and found increased levels of SRC-1 and VEGFC proteins in 13/20 and 15/20 thyroid cancer specimens, respectively, when compared with those levels in specimens of normal thyroid tissue. A high level of SRC-1 expression was positively correlated with VEGFC and lymphatic endothelial cell marker LYVE-1 expression. Papillary thyroid carcinoma cell line TPC-1 displayed high levels of SRC-1 and VEGFC expression and was selected for stable knockdown of SRC-1 in vitro. Inhibition of SRC-1 significantly reduced the VEGFC levels in TPC-1 cells. We found that SRC-1 binds to transcription factor NF-kB (p50/p65), and that this coactivation complex directly promoted VEGFC transcription, which could be abrogated by SRC-1 knockdown. Up-regulated NF-kB signaling was also confirmed in thyroid cancer tissues. In vivo studies showed that SRC-1 knockdown restricted tumor growth, reduced the numbers of LYVE-1-positive lymphatic vessels, and decreased the levels of VEGFC in tumor tissues. These results suggest a tumorigenic role for SRC-1 in thyroid cancer via its ability to regulate VEGFC expression.

Intermediate microRNA expression profile in Graves’ disease falls between that of normal thyroid tissue and papillary thyroid carcinoma

2016 ◽  
Vol 70 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Matthias Pohl ◽  
Florian Grabellus ◽  
Karl Worm ◽  
Georg Arnold ◽  
Martin Walz ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Thyroid Tissue ◽  
Fold Change ◽  
Graves Disease ◽  
Papillary Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Significant Difference ◽  
Benign Thyroid

AimsMany studies have previously reported a higher prevalence of papillary thyroid carcinomas (PTC) in patients with Graves' disease (GD). MicroRNAs (miRNAs) are small, non-coding RNAs that are upregulated in PTC compared with benign thyroid tissue. The objective of the study was to examine the miRNA expression of selected miRNAs that are known to be upregulated in PTC in patients with GD.MethodsParaffin embedded thyroid tissue from 159 patients with GD was screened for expression of the miRNAs 146b, 181b, 21, 221 and 222 by RT-PCR. The expression profiles of four normal thyroids, 50 PTCs without concomitant GD and 11 patients with untreated GD served as the controls.ResultsThe expression pattern of these miRNAs in patients with GD is intermediate between that of benign thyroid tissue (p<0.001) and PTC (in three out of five miRNAs, p<0.001). This corresponds to a 15-fold change for GD versus PTC, and a 31-fold change for GD versus normal thyroid tissue. The miRNA expression in 11 papillary microcarcinomas found in our study (a prevalence of 0.07) was not different from that in PTC samples from patients without GD for four of five miRNA types. Furthermore, we found a significant difference in the expression of miRNA 221/222 between treated and untreated GD tissue.ConclusionsIn conclusion, we found an intermediate expression of specific miRNAs in thyroid tissue from patients with GD that fell between the expression levels found in normal thyroid glands and PTC, which suggests a possible influence of certain miRNAs on developing PTC in patients with GD.

scholarly journals Quantitative and qualitative differences in protein expression between papillary thyroid carcinoma and normal thyroid tissue

2006 ◽  
Vol 45 (8) ◽  
pp. 613-626 ◽  
Author(s):  
Lewis M. Brown ◽  
Steve M. Helmke ◽  
Stephen W. Hunsucker ◽  
Romana T. Netea-Maier ◽  
Simon A. Chiang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Protein Expression ◽  
Thyroid Tissue ◽  
Papillary Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid

scholarly journals Expansion of inflammatory monocytes in periphery and infiltrated into thyroid tissue in Graves’ disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinxin Chen ◽  
Yanqiu Wang ◽  
Yicheng Qi ◽  
Jiqi Yan ◽  
Fengjiao Huang ◽  
...  
Keyword(s):  
Thyroid Tissue ◽  
Graves Disease ◽  
Thyrotropin Receptor ◽  
Monocyte Subsets ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Inflammatory Monocytes ◽  
B Cell Activating Factor ◽  
Thyrotropin Receptor Antibody

AbstractMonocytes are important mediators of immune system and are reported to be altered in autoimmune disorders. Little is known about the pathological role of monocytes in Graves’ disease (GD). Thus, we investigated monocytes in periphery and thyroid tissue in GD. Untreated GD patients were enrolled and followed up until remission. Monocytes were significantly increased and positively correlated with anti-thyrotropin receptor antibody (TRAb) in untreated GD (rcounts = 0.269, P < 0.001; rpercentage = 0.338, P < 0.001). Flow cytometry showed CD14++ CD16+ monocytes were increased and CD14++ CD16- monocytes were decreased in untreated GD (both P < 0.001). Skewed monocyte subsets were recovered in GD with remission. Serum B cell-activating factor (BAFF) was positively correlated with TRAb (r = 0.384 and P = 0.001). CD14++ CD16+ monocytes expressed higher level of BAFF in untreated GD (P < 0.05). The frequency of CD14+ monocytes and CD14+ CD16+ monocytes were significantly higher in GD thyroid tissue than in normal thyroid tissue (both P < 0.001). Our study suggested CD14++ CD16+ monocytes were significantly expanded and involved in the production of TRAb via secreting a higher level of BAFF in periphery. Besides, monocytes infiltrated into thyroid tissue and thus could serve as an important participant in GD pathogenesis.

Investigation of BK virus, Epstein-Barr virus and human papillomavirus sequences in postoperative thyroid gland specimens

2015 ◽  
Vol 30 (1) ◽  
pp. 104-110 ◽  
Author(s):  
Dimitris Stamatiou ◽  
Stavros P. Derdas ◽  
Emmanouil K. Symvoulakis ◽  
Georgios H. Sakorafas ◽  
Odysseas Zoras ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Epstein Barr Virus ◽  
Thyroid Tissue ◽  
Bk Virus ◽  
Gene Sequences ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Barr Virus ◽  
Epstein Barr ◽  
Tissue Specimens

Background Although recent evidence has implicated viruses in the regulation of epithelial-to-mesenchymal transition and tumor progression, little is known regarding viral infections in thyroid malignancies. Thus the aim of this study was to detect sequences of 3 potentially oncogenic viruses – BK virus (BKV), Epstein-Barr virus (EBV) and human papillomavirus (HPV) – in a series of postoperative thyroid gland specimens. Methods Thirty patients with thyroid nodules who underwent surgery for thyroid disease within a 3-year period were enrolled. Both nodular and adjacent normal thyroid tissue was surgically excised from each patient. Viral gene sequences of BKV (VP1), EBV (LMP1, EBNA2 and EBER1) and HPV were amplified by PCR. The PCR results were confirmed by direct sequencing analysis. Results VP1 gene sequences were detected in 60% (18/30) of thyroid cancer or multinodular hyperplasia lesions compared with in 43.3% (13/30) of adjacent normal thyroid tissue specimens. Fifteen of thirty (50%) of thyroid cancer or multinodular hyperplasia samples revealed LMP1 sequences compared with 46.7% (14/30) of corresponding normal thyroid tissues. EBNA2 gene sequences were detected in 90% (27/30) of thyroid cancer or multinodular hyperplasia samples, compared with 90% (27/30) of adjacent normal thyroid tissue specimens. All samples were negative for EBER1 sequences, while HPV DNA was not detected in either nodular or normal thyroid tissue. Conclusions This study suggests that BKV and EBV “infection” is an early event, occurring within normal tissue. Our findings do not show a clear role for the viruses examined, instead they suggest an “endemicity” pattern rather than a causal effect.

scholarly journals SQSTM1/p62 Promotes Cell Growth and Triggers Autophagy in Papillary Thyroid Cancer by Regulating the AKT/AMPK/mTOR Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Fangqin Yu ◽  
Runsheng Ma ◽  
Chenguang Liu ◽  
Lele Zhang ◽  
Kaixiang Feng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Cell Growth ◽  
Cell Line ◽  
Papillary Thyroid Cancer ◽  
Cell Lines ◽  
Papillary Thyroid ◽  
Mtor Signaling Pathway ◽  
Normal Thyroid

BackgroundThyroid cancer is one of the most common endocrine malignancies worldwide, and papillary thyroid cancer (PTC) is the most common pathologic type of thyroid cancer. SQSTM1/p62 activity mediates different biological functions. This study aimed to investigate the effect of SQSTM1/p62, a multifunctional receptor, on biological function and autophagy characteristics in the human PTC cell line TPC-1.MethodsA total of 105 primary PTC samples and matched adjacent normal thyroid tissue samples were obtained to evaluate the expression of p62 in clinical patients. A similar p62 expression pattern was found in PTC cell lines and normal human thyroid follicular epithelial cells. To evaluate the effect of SQSTM1/p62 on TPC-1 cells, we constructed the p62 knockout cell line p62-KO-TPC-1. Cell proliferation, cell cycle, and cell apoptosis were analyzed by colony formation tests, Cell Counting Kit-8 (CCK-8) assays and flow cytometry in vitro. TPC-1 and p62-KO-TPC-1 human PTC cell lines in the logarithmic growth phase were subcutaneously implanted into BALB/c nude mice to verify their proliferation effect in vivo. Furthermore, western blotting and immunohistochemistry (IHC) were used to detect the expression of AKT/AMPK/mTOR signaling pathway-related proteins.ResultsOverall, p62 expression was higher in tumor tissues than in normal tissues in 73 of 105 PTC patients (69.5%). The expression level of p62 in the PTC cell line was higher than that in the normal thyroid cell line. Our data indicated that in vitro, p62 deficiency could decrease the number of colonies, inhibit cell growth and the cell cycle, and induce apoptosis. Tumor xenograft experiments in BALB/c nude mice corroborated these findings. Moreover, the molecular mechanism was explored by western blotting, and we found that the AMPK/AKT/mTOR pathway was involved.ConclusionsThe results indicate that p62 might mediate cell autophagy and apoptosis in TPC-1 cells via the AMPK/AKT/mTOR pathway and could be used as a potential therapeutic approach for PTC.

scholarly journals Low expression of Met-hepatocytic growth factor receptor as an indicator of poor prognosis in thyroid tumors

2001 ◽  
Vol 47 (3) ◽  
pp. 6-10 ◽  
Author(s):  
I. I. Dedov ◽  
Ye. A. Troshina ◽  
N. V. Mazurina ◽  
A. Belfiore
Keyword(s):  
Growth Factor ◽  
Poor Prognosis ◽  
Thyroid Tissue ◽  
Growth Factor Receptor ◽  
Immunohistochemical Method ◽  
Papillary Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Cell Staining ◽  
Low Expression

Clinical implication of Met-hepatocytic growth factor receptor (Met/HGF-R) in thyroid adenocarcinoma tissue was studied on 163 operative thyroid samples (129papillary cancers, 21 follicular cancers, and 13 anaplastic cancers). 49 adenomas, 50 nodular goiters and 50 normal thyroids were compared. Expression of Met/HGF-R was estimated using semiquantitative immunohistochemical method including proportion (limits 0-5) and intensity (limits 0-5) of cell staining and calculation of Met/HGF-R total expression (limit 0-10). Met/HGF-R was not found in normal thyroid tissue, was absent or focally expressed in follicular and aplastic tumors, and was present in different amounts in papillary adenocarcinomas. It is suggested that low expression of Met/HGF-R is an indicator of unfavorable prognosis in papillary thyroid cancer.

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