1. Cancer Stem Cells in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System.
- Author
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Siljee S, Buchanan O, Brasch HD, Bockett N, Patel J, Paterson E, Purdie GL, Davis PF, Itinteang T, and Tan ST
- Subjects
- Aged, Aged, 80 and over, Angiotensin-Converting Enzyme 2 genetics, Angiotensin-Converting Enzyme 2 metabolism, Angiotensinogen genetics, Angiotensinogen metabolism, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms blood supply, Head and Neck Neoplasms genetics, Humans, Microvessels metabolism, Middle Aged, Neoplasm Metastasis, Receptor, Angiotensin, Type 1 genetics, Receptor, Angiotensin, Type 1 metabolism, Receptor, Angiotensin, Type 2 genetics, Receptor, Angiotensin, Type 2 metabolism, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism, Renin genetics, Renin metabolism, Squamous Cell Carcinoma of Head and Neck blood supply, Squamous Cell Carcinoma of Head and Neck genetics, Stromal Cells metabolism, Stromal Cells pathology, Prorenin Receptor, Head and Neck Neoplasms metabolism, Head and Neck Neoplasms pathology, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Renin-Angiotensin System genetics, Squamous Cell Carcinoma of Head and Neck metabolism, Squamous Cell Carcinoma of Head and Neck pathology
- Abstract
We investigated the expression of components of the renin-angiotensin system (RAS) by cancer stem cell (CSC) subpopulations in metastatic head and neck cutaneous squamous cell carcinoma (mHNcSCC). Immunohistochemical staining demonstrated expression of prorenin receptor (PRR), angiotensin-converting enzyme (ACE), and angiotensin II receptor 2 (AT
2 R) in all cases and angiotensinogen in 14 cases; however, renin and ACE2 were not detected in any of the 20 mHNcSCC tissue samples. Western blotting showed protein expression of angiotensinogen in all six mHNcSCC tissue samples, but in none of the four mHNcSCC-derived primary cell lines, while PRR was detected in the four cell lines only. RT-qPCR confirmed transcripts of angiotensinogen, PRR, ACE, and angiotensin II receptor 1 (AT1 R), but not renin or AT2 R in all four mHNcSCC tissue samples and all four mHNcSCC-derived primary cell lines, while ACE2 was expressed in the tissue samples only. Double immunohistochemical staining on two of the mHNcSCC tissue samples showed expression of angiotensinogen by the SOX2+ CSCs within the tumor nests (TNs), and immunofluorescence showed expression of PRR and AT2 R by the SOX2+ CSCs within the TNs and the peritumoral stroma (PTS). ACE was expressed on the endothelium of the tumor microvessels within the PTS. We demonstrated expression of angiotensinogen by CSCs within the TNs, PRR, and AT2 R by the CSCs within the TNs and the PTS, in addition to ACE on the endothelium of tumor microvessels in mHNcSCC.- Published
- 2021
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