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Alteration of primary cilia morphology and associated signalling in ameloblastoma

J. Filušová, I. Putnová, P. Hurník, Z. Daněk, C. Macháček, . Jan Štembírek, M. Buchtová, B. Moldovan Putnová

. 2022 ; 142 (-) : 105499. [pub] 20220704

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024230

OBJECTIVES: Primary cilium is a cellular organelle with growing significance confirmed in tumour biology. Primary cilia have been associated with fine tuning of numerous cell signalling pathways and the role of this structure in cancer initiation and progression is recently at the forefront of attention. Here, we investigated possible alterations in the occurrence of primary cilia and changes of associated signalling in ameloblastoma, which represents the most common odontogenic tumour. METHODS: We performed immunohistochemistry to assess the number and morphology of primary cilia in ameloblastoma tissues. The gene expression of key SHH pathway members was analysed by qPCR. As a functional experiment, we treated a primary ameloblastoma cell line by a SHH pathway inhibitor Sonidegib (LDE225). RESULTS: We uncovered differences in primary cilia distribution and appearance in histological subtypes of ameloblastoma with the highest number of ciliated cells in plexiform and follicular subtypes. SHH protein was located close to primary cilia in ameloblastoma epithelial cells and the expression of molecules downstream of SHH signalling was upregulated. Moreover, the inhibition of SHH pathway by Sonidegib caused downregulation of SHH effector gene GLI1 and cell cycle regulator CCND1 in ameloblastoma primary cell line. The inhibition of SHH signalling also altered the expression of molecules involved in intraflagellar transport. CONCLUSIONS: In conclusion, our study uncovered alterations in number of ciliated cells and associated signalling in ameloblastoma, which indicate SHH inhibitors as potential therapeutic target to treat this disease.

Citace poskytuje Crossref.org

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$a OBJECTIVES: Primary cilium is a cellular organelle with growing significance confirmed in tumour biology. Primary cilia have been associated with fine tuning of numerous cell signalling pathways and the role of this structure in cancer initiation and progression is recently at the forefront of attention. Here, we investigated possible alterations in the occurrence of primary cilia and changes of associated signalling in ameloblastoma, which represents the most common odontogenic tumour. METHODS: We performed immunohistochemistry to assess the number and morphology of primary cilia in ameloblastoma tissues. The gene expression of key SHH pathway members was analysed by qPCR. As a functional experiment, we treated a primary ameloblastoma cell line by a SHH pathway inhibitor Sonidegib (LDE225). RESULTS: We uncovered differences in primary cilia distribution and appearance in histological subtypes of ameloblastoma with the highest number of ciliated cells in plexiform and follicular subtypes. SHH protein was located close to primary cilia in ameloblastoma epithelial cells and the expression of molecules downstream of SHH signalling was upregulated. Moreover, the inhibition of SHH pathway by Sonidegib caused downregulation of SHH effector gene GLI1 and cell cycle regulator CCND1 in ameloblastoma primary cell line. The inhibition of SHH signalling also altered the expression of molecules involved in intraflagellar transport. CONCLUSIONS: In conclusion, our study uncovered alterations in number of ciliated cells and associated signalling in ameloblastoma, which indicate SHH inhibitors as potential therapeutic target to treat this disease.
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$a Putnová, Iveta $u Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic; Department of Anatomy, Histology and Embryology, University of Veterinary Sciences Brno, Brno, Czech Republic
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$a Hurník, Pavel $u Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic; Department of Clinical and Molecular Pathology and Medical Genetics, Faculty of Medicine and University Hospital Ostrava, Ostrava, Czech Republic; Department of Histology and Embryology, Medical Faculty, Masaryk University, Brno, Czech Republic
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$a Daněk, Zdeněk $u Department of Maxillofacial Surgery, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; RECETOX, Faculty of Science, Masaryk University, Kotlarska 2, Brno, Czech Republic
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$a Macháček, Ctirad $u Department of Pathology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Jan Štembírek, $u Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic; Department of Maxillofacial Surgery, University Hospital Ostrava, Ostrava, Czech Republic
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$a Buchtová, Marcela $u Laboratory of Molecular Morphogenesis, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
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