Cancer Stem Cells in Head and Neck Cutaneous Squamous Cell Carcinoma Express Cathepsins

Therese Featherston1, Helen D Brasch1, Sam D Siljee1

  • 1Gillies McIndoe Research Institute, Newtown, Wellington, New Zealand.

Insights

Cancer stem cells in head and neck squamous cell carcinoma express cathepsins B, D, and G. Functionally active cathepsins B and D are found in cancer stem cells, suggesting potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer stem cells (CSCs) drive tumor growth and recurrence in head and neck cutaneous squamous cell carcinoma (HNSCC).
  • The renin-angiotensin system (RAS) components are expressed by CSCs in HNSCC.
  • Cathepsins B, D, and G act as bypass loops within the RAS, potentially influencing CSC behavior.

Purpose of the Study:

  • To investigate the expression and localization of cathepsins B, D, and G in CSC subpopulations within moderately differentiated HNSCC (MDHNcSCC).
  • To determine the functional activity of these cathepsins in MDHNcSCC.
  • To explore the potential of targeting these cathepsins for HNSCC therapy.

Main Methods:

  • Immunohistochemistry and immunofluorescence staining of MDHNcSCC tissue samples (n=15) to detect cathepsin expression and co-localization with CSC markers (OCT4, c-MYC).
  • Reverse transcription quantitative polymerase chain reaction (RT-qPCR) to analyze cathepsin transcript expression in MDHNcSCC tissues (n=5).
  • Western blotting and enzymatic activity assays on MDHNcSCC tissues (n=5) and cell lines (n=6) to confirm protein expression and functional activity.

Main Results:

  • Cathepsins B, D, and G were expressed in all MDHNcSCC tissue samples.
  • Cathepsins B and D were localized to OCT4+ and c-MYC+ CSC subpopulations in tumor nests and stroma.
  • Cathepsin G was found on tryptase+/c-MYC+ cells in the peritumoral stroma, with confirmed transcript and protein expression and functional activity for cathepsins B and D.

Conclusions:

  • Cathepsins B, D, and G are expressed in MDHNcSCC, with functionally active cathepsins B and D associated with CSCs.
  • Cathepsin G expression is linked to mast cells in the tumor microenvironment.
  • Inhibitors targeting cathepsins, in conjunction with RAS blockade, represent a potential therapeutic strategy against CSCs in MDHNcSCC.

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