Cancer Stem Cells in Head and Neck Cutaneous Squamous Cell Carcinoma Express Cathepsins
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Methods: Immunohistochemical staining was performed on MDHNcSCC tissue samples from 15 patients to determine the expression of cathepsins B, D, and G. Co-localization of these cathepsins with the embryonic stem cell markers Octamer-binding transcription factor 4 (OCT4) and c-MYC was investigated with immunofluorescence staining. Reverse transcription quantitative polymerase chain reaction was performed on 5 MDHNcSCC tissue samples to investigate transcript expression of cathepsins B, D and G. Western blotting and enzymatic activity assays were performed on 5 MDHNcSCC tissue samples and 6 MDHNcSCC-derived primary cell lines to confirm protein expression, transcript expression, and functional activity of these cathepsins, respectively.
Results: Immunohistochemical staining demonstrated the expression of cathepsins B, D, and G in all MDHNcSCC tissue samples. Immunofluorescence staining showed localization of cathepsins B and D to the c-MYC CSC subpopulations and the OCT4 CSC subpopulations within the tumor nests and the peritumoral stroma. Cathepsin G was expressed on the tryptase/c-MYC cells within the peritumoral stroma. Reverse transcription quantitative polymerase chain reaction demonstrated transcript expression of cathepsins B, D and G in the MDHNcSCC tissue samples. Western blotting and enzymatic activity assays confirmed protein expression and functional activity of cathepsins B and D in the MDHNcSCC tissue samples and MDHNcSCC-derived primary cell lines, respectively.
Conclusions: Cathepsins B, D, and G are expressed in MDHNcSCC with functionally active cathepsins B and D localizing to the CSC subpopulations, and cathepsin G is expressed by mast cells, suggesting the potential use of cathepsin inhibitors in addition to RAS blockade to target CSCs in MDHNcSCC.
Lee Y, Lee L, Huang Y, Kao H, Chang Y, Hung S Laryngoscope Investig Otolaryngol. 2023; 8(6):1547-1556.
PMID: 38130271 PMC: 10731513. DOI: 10.1002/lio2.1166.
The Role of Cathepsin B in Pathophysiologies of Non-tumor and Tumor tissues: A Systematic Review.
Wang J, Zheng M, Yang X, Zhou X, Zhang S J Cancer. 2023; 14(12):2344-2358.
PMID: 37576397 PMC: 10414043. DOI: 10.7150/jca.86531.
Kilmister E, Koh S, Weth F, Gray C, Tan S Biomedicines. 2022; 10(11).
PMID: 36428556 PMC: 9687343. DOI: 10.3390/biomedicines10112988.
Munday J, Odom T, Dittmer K, Wetzel S, Hillmer K, Tan S Vet Sci. 2022; 9(8).
PMID: 36006326 PMC: 9413835. DOI: 10.3390/vetsci9080411.
[Research progress of cancer stem cell biomarkers in head and neck squamous cell carcinoma].
Li M, Gao W, Wu Y, Guo P, Qin Y, Wang W Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2021; 35(9):854-858.
PMID: 34628845 PMC: 10127838. DOI: 10.13201/j.issn.2096-7993.2021.09.020.