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Updated: Nov 19, 2025

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
Cancer Stem Cells in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the
Sam Siljee1, Olivia Buchanan1, Helen D Brasch1
1Gillies McIndoe Research Institute, Wellington 6242, New Zealand.
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 (AT2R) 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 (AT1R), but not renin or AT2R 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 AT2R 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 AT2R by the CSCs within the TNs and the PTS, in addition to ACE on the endothelium of tumor microvessels in mHNcSCC.
Insights
Cancer stem cells in head and neck squamous cell carcinoma express key renin-angiotensin system components like angiotensinogen and prorenin receptor. This suggests potential roles for the renin-angiotensin system in mHNcSCC progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Metastatic head and neck cutaneous squamous cell carcinoma (mHNcSCC) is an aggressive malignancy.
- Cancer stem cells (CSCs) are implicated in tumor initiation, metastasis, and therapeutic resistance.
- The renin-angiotensin system (RAS) plays roles in various physiological and pathological processes, including cancer.
Purpose of the Study:
- To investigate the expression of renin-angiotensin system (RAS) components within cancer stem cell (CSC) subpopulations in mHNcSCC.
- To determine the cellular localization of RAS components in relation to CSCs and tumor microenvironment.
Main Methods:
- Immunohistochemistry and immunofluorescence staining of mHNcSCC tissue samples.
- Western blotting analysis of mHNcSCC tissue and primary cell lines.
- RT-qPCR to analyze gene expression of RAS components.
Main Results:
- Expression of prorenin receptor (PRR), angiotensin-converting enzyme (ACE), and angiotensin II receptor 2 (AT2R) was detected in mHNcSCC tissues.
- Angiotensinogen was expressed by SOX2+ CSCs within tumor nests; PRR and AT2R were also expressed by CSCs in tumor nests and peritumoral stroma.
- ACE was localized to the endothelium of tumor microvessels; renin and ACE2 were generally not detected.
Conclusions:
- Cancer stem cells in mHNcSCC express key components of the renin-angiotensin system, including angiotensinogen, PRR, and AT2R.
- The findings suggest a potential role for the RAS in regulating CSC behavior and the tumor microenvironment in mHNcSCC.
- Targeting RAS components may offer novel therapeutic strategies for mHNcSCC.
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