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Updated: May 9, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Expression of hedgehog signalling pathway in anaplastic thyroid cancer
Ulrike Hinterseher1, Annette Wunderlich, Silvia Roth
1Department of Visceral, Thoracic- and Vascular Surgery, University Hospital Marburg, Baldingerstrasse, 35043, Marburg, Germany.
Abstract:
The purpose of this work is to study the activation of the hedgehog signalling pathway is associated with tumour progression in various types of cancer, hence the development of specific antagonists raises hope for new therapeutic strategies. Therefore, the expression of hedgehog pathway components in anaplastic thyroid cancer (ATC) and effects of the hedgehog inhibitor Cyclopamine on ATC cells were investigated in this study. Expression of the ligand Sonic Hedgehog (SHh), the transmembrane protein Smoothened (Smo), the receptor Patched (Ptc) and the target gene Gli-1 was evaluated in two ATC cell lines (Hth 74, C643) by RT-PCR and in tumour specimens by immunohistochemistry. The corresponding gene products were examined by western blotting analysis. After treatment with different concentrations of Cyclopamine the time-dependent course of cell viability in ATC cell lines was evaluated by MTT assay. SHh, Smo, Ptc and Gli were clearly expressed on mRNA and protein levels in both cell lines and in tumour samples (41 %SHh, 65 %Smo, 65 %Ptc and 65 %Gli). Treatment with Cyclopamine showed a time- and dose-dependent inhibition of cell numbers with IC50 values between 1 and 4 μM in both cell lines, comparable to other types of cancer. In conclusion, we believe that the hedgehog pathway is expressed in anaplastic thyroid carcinoma specimens and proliferation of ATC cell lines can be influenced by the Hh inhibitor Cyclopamine. Aberrant activation of this pathway might be involved in the aggressive biology of anaplastic cancer and further evaluation regarding a possible clinical impact of pathway inhibition is warranted.
Insights
The hedgehog signalling pathway is active in anaplastic thyroid cancer (ATC). Inhibiting this pathway with Cyclopamine reduced ATC cell proliferation, suggesting a potential therapeutic target for this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The hedgehog signalling pathway plays a role in tumour progression across various cancers.
- Specific antagonists targeting this pathway offer potential therapeutic strategies.
- Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited treatment options.
Purpose of the Study:
- To investigate hedgehog pathway component expression in ATC.
- To determine the effects of the hedgehog inhibitor Cyclopamine on ATC cell lines.
Main Methods:
- RT-PCR and immunohistochemistry were used to evaluate gene and protein expression of Sonic Hedgehog (SHh), Smoothened (Smo), Patched (Ptc), and Gli-1 in ATC cell lines and tumour specimens.
- Western blotting analyzed gene product levels.
- MTT assays assessed cell viability after Cyclopamine treatment.
Main Results:
- SHh, Smo, Ptc, and Gli were expressed at both mRNA and protein levels in ATC cell lines and tumour samples.
- Cyclopamine treatment resulted in time- and dose-dependent inhibition of ATC cell proliferation.
- The IC50 values for Cyclopamine ranged from 1 to 4 μM in both tested cell lines.
Conclusions:
- The hedgehog pathway is expressed in anaplastic thyroid carcinoma.
- Inhibition of the hedgehog pathway with Cyclopamine affects ATC cell proliferation.
- Aberrant hedgehog pathway activation may contribute to the aggressive nature of ATC, warranting further clinical investigation.
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