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Article

Cancer Stem Cells in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System

1
Gillies McIndoe Research Institute, Wellington 6242, New Zealand
2
Biostatistical Group, Dean’s Department, University of Otago, Wellington 6021, New Zealand
3
Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Lower Hutt 5010, New Zealand
4
Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC 3050, Australia
*
Author to whom correspondence should be addressed.
These authors have contributed the same to the manuscript.
Academic Editor: András Balla
Cells 2021, 10(2), 243; https://doi.org/10.3390/cells10020243
Received: 13 December 2020 / Revised: 13 January 2021 / Accepted: 22 January 2021 / Published: 27 January 2021
(This article belongs to the Special Issue Renin–Angiotensin–Aldosterone System)
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. View Full-Text
Keywords: cutaneous squamous cell carcinoma; cancer stem cells; angiotensinogen; renin; prorenin receptor; angiotensin-converting enzyme; angiotensin-converting enzyme 2; angiotensin II receptor 1; angiotensin II receptor 2 cutaneous squamous cell carcinoma; cancer stem cells; angiotensinogen; renin; prorenin receptor; angiotensin-converting enzyme; angiotensin-converting enzyme 2; angiotensin II receptor 1; angiotensin II receptor 2
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MDPI and ACS Style

Siljee, S.; Buchanan, O.; Brasch, H.D.; Bockett, N.; Patel, J.; Paterson, E.; Purdie, G.L.; Davis, P.F.; Itinteang, T.; Tan, S.T. Cancer Stem Cells in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System. Cells 2021, 10, 243. https://doi.org/10.3390/cells10020243

AMA Style

Siljee S, Buchanan O, Brasch HD, Bockett N, Patel J, Paterson E, Purdie GL, Davis PF, Itinteang T, Tan ST. Cancer Stem Cells in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System. Cells. 2021; 10(2):243. https://doi.org/10.3390/cells10020243

Chicago/Turabian Style

Siljee, Sam, Olivia Buchanan, Helen D. Brasch, Nicholas Bockett, Josie Patel, Erin Paterson, Gordon L. Purdie, Paul F. Davis, Tinte Itinteang, and Swee T. Tan. 2021. "Cancer Stem Cells in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System" Cells 10, no. 2: 243. https://doi.org/10.3390/cells10020243

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