scholarly journals Secreted Factors by Anaplastic Thyroid Cancer Cells Induce Tumor-Promoting M2-like Macrophage Polarization through a TIM3-Dependent Mechanism

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4821
Author(s):  
Cinthia Carolina Stempin ◽  
Romina Celeste Geysels ◽  
Sunmi Park ◽  
Luz Maria Palacios ◽  
Ximena Volpini ◽  
...  

Anaplastic thyroid cancer (ATC) is a highly aggressive type of thyroid cancer (TC). Currently, no effective target treatments are available that can improve overall survival, with ATC representing a major clinical challenge because of its remarkable lethality. Tumor-associated macrophages (TAMs) are the most evident cells in ATCs, and their high density is correlated with a poor prognosis. However, the mechanisms of how TAMs promote ATC progression remain poorly characterized. Here, we demonstrated that the treatment of human monocytes (THP-1 cells) with ATC cell-derived conditioned media (CM) promoted macrophage polarization, showing high levels of M2 markers. Furthermore, we found that STAT3 was activated, and this was correlated with an increased expression and secretion of the inflammatory cytokine interleukin-6. Remarkably, the M2-like macrophages obtained revealed tumor-promoting activity. A cytokine array analysis demonstrated that M2-like macrophage-derived CM contained high levels of TIM3, which is an important immune regulatory molecule. Consistently, TIM3 expression was up-regulated in THP-1 cells cultured with ATC cell-derived CM. Moreover, TIM3 blockade significantly reversed the polarization of THP-1 cells induced by ATC cell-secreted soluble factors. We validated the clinical significance of the TIM3 in human TC by analyzing public datasets and found that the expression of TIM3 and its ligand galectin 9 was significantly higher in human TC tissue samples than in normal thyroid tissues. Taken together, our findings identified a new mechanism by which TIM3 induces tumor-promoting M2-like macrophage polarization in TC. Furthermore, TIM3 interference might be a potential tool for treatment of patients with ATC.

2021 ◽  
Author(s):  
Zhenzhen Li ◽  
Xiong Chaoliang ◽  
Jin Wei ◽  
Ping Chen ◽  
Yanping Zhang ◽  
...  

Abstract Background Anaplastic thyroid cancer (ATC) has a high degree of malignancy and a poor prognosis. Its incidence accounts for approximately 10–15% of all thyroid cancers. The purpose of this study was to determine the differentially expressed genes (DEGs) of ATC through biometric analysis technology, clarify the potential interactions between them, and screen genes related to the prognosis of ATC. Methods The GSE29265, GSE65144, GSE33630, and GSE85457 expression profiles downloaded from the Gene Expression Omnibus database (GEO) contained a total of 117 tissue samples (81 normal thyroid tissue samples and 36 ATC samples). The four datasets were integrated and analyzed by the limma packages to obtain DEGs. With these DEGs, we performed gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses using the Database for Annotation, Visualization and Integrated Discovery, protein-protein interaction (PPI) analysis using Cytoscape, and survival analysis using the Kaplan-Meier (KM) plotter. Results. After R integration analysis of the four datasets, 764 DEGs were obtained, i.e., 314 upregulated and 450 downregulated genes. Among the hub DEGs obtained in the PPI network, the expression levels of thymidylate synthase (TYMS), fibronectin 1, chordin-like 1, syndecan 2, integrin alpha 2, collagen type I alpha 1 chain, collagen type IX alpha 3 chain (COL9A3), and collagen type XXIII alpha 1 chain (COL23A1) were associated with ATC prognosis. These results showed that the overall survival and recurrence-free survival of TYMS, COL9A3, and COL23A1 were statistically significant in our KM plotter survival analysis; thus, these DEGs may be used as potential biomarkers of ATC. Conclusion This study identified several potential target genes and pathways that may affect the development of ATC. These findings provide new insights for the detection of novel diagnostic and therapeutic biomarkers for ATC.


2005 ◽  
Vol 90 (6) ◽  
pp. 3583-3591 ◽  
Author(s):  
Jingxuan Pan ◽  
Huizhi Huang ◽  
Lily Sun ◽  
Bingliang Fang ◽  
Sai-Ching Jim Yeung

2020 ◽  
Vol 49 (24) ◽  
pp. 8375-8388
Author(s):  
Denise Lovison ◽  
Lorenzo Allegri ◽  
Federica Baldan ◽  
Maurizio Ballico ◽  
Giuseppe Damante ◽  
...  

High cytotoxic and antimetastatic activities against anaplastic thyroid cancer are displayed by cationic complexes [RuX(CO)(dppb)(phen)]Y (X = Y = OAc, OPiv, SAc, and NCS; X = Cl and Y = PF6).


2017 ◽  
Author(s):  
Shuzo Tamura ◽  
Takashi Oshima ◽  
Mariko Kamiya ◽  
Shinya Amano ◽  
Toru Aoyama ◽  
...  

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