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Wickremesekera et al. J Cancer Metastasis Treat 2019;5:62 Journal of Cancer
DOI: 10.20517/2394-4722.2019.09 Metastasis and Treatment

Original Article Open Access

Cancer stem cell subpopulations in metastatic
melanoma to the brain express components of the

renin-angiotensin system

Agadha C. Wickremesekera , Helen D. Brasch , Valerie M. Lee , Paul F. Davis , Andrew Parker , Helge
1,2
2
1
1
1
Koeck , Tinte Itinteang , Swee T. Tan 1,3#
2
1#
1 Gillies McIndoe Research Institute, Wellington 6242, New Zealand.
2 Department of Neurosurgery, Wellington Regional Hospital, Wellington 6021, New Zealand.
3 Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, Lower Hutt 5010, New Zealand.
# Equal senior authors.
Correspondence to: Dr. Swee T Tan, Gillies McIndoe Research Institute, PO Box 7184, Newtown, Wellington 6242, New Zealand.
E-mail: swee.tan@gmri.org.nz
How to cite this article: Wickremesekera AC, Brasch HD, Lee VM, Davis PF, Parker A, Koeck H, Itinteang T, Tan ST. Cancer
stem cell subpopulations in metastatic melanoma to the brain express components of the renin-angiotensin system. J Cancer
Metastasis Treat 2019;5:62. http://dx.doi.org/10.20517/2394-4722.2019.09
Received: 29 Apr 2019 First Decision: 11 Jul 2019 Revised: 11 Jul 2019 Accepted: 6 Aug 2019 Published: 27 Aug 2019

Science Editor: Ira-Ida Skvortsova Copy Editor: Jia-Jia Meng Production Editor: Jing Yu

Abstract
Aim: There is increasing appreciation of the role of the renin-angiotensin system (RAS) in carcinogenesis with
recent evidence showing expression of the RAS by cancer stem cells (CSCs) in different types of cancer. We have
recently demonstrated the presence of three CSC subpopulations within metastatic melanoma (MM) to the brain:
a Melan-A subpopulation and a Melan-A subpopulation within the tumor that express OCT4, SALL4, SOX2 and
+
-
NANOG; and a pSTAT3 subpopulation localized to the CD34 endothelium of microvessels within the tumor. In this
+
+
study we investigated the expression and localization of components of the RAS in relation to these CSCs in MM
to the brain.
Methods: 3, 3-diaminobenzidine immunohistochemical (IHC) staining of components of the RAS: pro-renin receptor
(PRR), angiotensin converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1) and angiotensin II receptor 2 (ATIIR2)
was performed on the same ten samples of MM to the brain included in our previous study. Immunofluorescence
IHC staining of these components of the RAS was performed with embryonic stem cell markers OCT4 and NANOG,
and endothelial marker CD34, on two of the samples of MM to the brain from the original cohort of ten patients.
Western blotting (n = 5) and NanoString mRNA analysis (n = 4) were performed on samples of MM to the brain to
confirm protein and mRNA expression of these components of the RAS, respectively.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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