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Narayanan et al. J Cancer Metastasis Treat 2019;5:36 Journal of Cancer
DOI: 10.20517/2394-4722.2018.77 Metastasis and Treatment

Original Article Open Access

Cancer stem cells in liver metastasis from colon
adenocarcinoma express components of the renin-

angiotensin system

Anantha Narayanan , Susrutha K. Wickremesekera , Bede van Schaijik , Reginald W. Marsh , Helen D.
1,2
1,2
1
1,3
Brasch , Swee T. Tan 1,4,# , Tinte Itinteang 1,#
1
1 Gillies McIndoe Research Institute, Wellington 6242, New Zealand.
2 Upper Gastrointestinal, Hepatobiliary & Pancreatic Section, Department of General Surgery, Wellington Regional Hospital,
Wellington 6242, New Zealand.
3 University of Auckland, Auckland 1010, New Zealand.
4 Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington 6242, New Zealand.
# Authors contributed equally.
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: Narayanan A, Wickremesekera SK, van Schaijik B, Marsh RW, Brasch HD, Tan ST, Itinteang T. Cancer
stem cells in liver metastasis from colon adenocarcinoma express components of the renin-angiotensin system. J Cancer
Metastasis Treat 2019;5:36. http://dx.doi.org/10.20517/2394-4722.2018.77

Received: 20 Nov 2018 First Decision: 19 Jan 2019 Revised: 9 Feb 2019 Accepted: 28 Feb 2019 Published: 24 Apr 2019

Science Editor: Guo-Feng Xie Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Aim: We have recently identified a cancer stem cell (CSC) subpopulations within the tumor nests (TNs) and another
within the peritumoral stroma (PTS) in liver metastasis from colon adenocarcinoma (LMCA). This study investigated
the expression of components of the renin-angiotensin (RAS): pro-renin receptor (PRR), angiotensin converting
enzyme (ACE), and angiotensin II receptor 1 (ATIIR1) and angiotensin II receptor 2 (ATIIR2) in LMCA.

Methods: 3,3-Diaminobenzidine (DAB) immunohistochemical (IHC) staining was performed on 16 LMCA samples
for PRR, ACE, ATIIR1 and ATIIR2. Immunofluorescence (IF) IHC staining was performed to investigate co-expression
of these components of the RAS with SOX2 or OCT4. NanoString analysis ( n = 6) and Western blotting (WB, n = 3)
were performed on snap-frozen LMCA samples to confirm mRNA and protein expression, respectively.

Results: DAB IHC staining showed the expression of PRR, ACE, ATIIR1 and ATIIR2 within all LMCA samples.
NanoString analysis and WB confirmed gene and protein expression of these components of the RAS. IF IHC staining
+
+
demonstrated expression of PRR, ATIIR1 and ATIIR2 by the SOX2 CSCs within the TNs and the OCT4 CSCs within
the PTS. ACE was expressed on the endothelium of the microvessels within the PTS.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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