AUTHOR=Humphries Hugo N. , Wickremesekera Susrutha K. , Marsh Reginald W. , Brasch Helen D. , Mehrotra Shreeja , Tan Swee T. , Itinteang Tinte 

TITLE=Characterization of Cancer Stem Cells in Colon Adenocarcinoma Metastasis to the Liver

JOURNAL=Frontiers in Surgery

VOLUME=4

YEAR=2018

URL=https://www.frontiersin.org/journals/surgery/articles/10.3389/fsurg.2017.00076

DOI=10.3389/fsurg.2017.00076

ISSN=2296-875X

ABSTRACT=<sec id="ST1"><title>Background</title><p>Fifty percent of colorectal cancer (CRC) patients develop liver metastasis. This study identified and characterized cancer stem cells (CSCs) within colon adenocarcinoma metastasis to the liver (CAML).</p></sec><sec id="ST2"><title>Methods</title><p>3,3-Diaminobenzidine immunohistochemical (IHC) staining was performed on nine CAML samples for embryonic stem cell (ESC) markers OCT4, SOX2, NANOG, c-Myc, and KLF4. Immunofluorescence (IF) IHC staining was performed to investigate coexpression of two markers. NanoString mRNA expression analysis and colorimetric <italic>in situ</italic> hybridization (CISH) were performed on four snap-frozen CAML tissue samples for transcript expression of these ESC markers. Cells stained positively and negatively for each marker by IHC and CISH staining were counted and analyzed.</p></sec><sec id="ST3"><title>Results</title><p>3,3-Diaminobenzidine IHC staining, and NanoString and CISH mRNA analyses demonstrated the expression of OCT4, SOX2, NANOG, c-Myc, and KLF4 within in all nine CAML samples, except for SOX2 which was below detectable levels on NanoString mRNA analysis. IF IHC staining showed the presence of a SOX2<sup>+</sup>/NANOG<sup>+</sup>/KLF4<sup>+</sup>/c-Myc<sup>+</sup>/OCT<sup>−</sup> CSC subpopulation within the tumor nests, and a SOX2<sup>+</sup>/NANOG<sup>+</sup>/KLF4<sup>+</sup>/c-Myc<sup>+</sup>/OCT4<sup>−</sup> CSC subpopulation and a SOX2<sup>+</sup>/NANOG<sup>+</sup>/KLF4<sup>+</sup>/c-Myc<sup>+</sup>/OCT4<sup>+</sup> CSC subpopulation within the peritumoral stroma.</p></sec><sec id="ST4"><title>Conclusion</title><p>The novel finding of three CSC subpopulations within CAML provides insights into the biology of CRC.</p></sec>