Cancer stem cell subpopulations in primary colon adenocarcinoma
Author(s) -
Matthew J. Munro,
Susrutha K. Wickremesekera,
Lifeng Peng,
Reginald Marsh,
Tinte Itinteang,
Swee T. Tan
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0221963
Subject(s) - homeobox protein nanog , sox2 , klf4 , cancer stem cell , biology , stromal cell , induced pluripotent stem cell , stem cell marker , cancer research , stem cell , population , pathology , nanog homeobox protein , adenocarcinoma , colorectal cancer , cancer , embryonic stem cell , medicine , microbiology and biotechnology , genetics , gene , environmental health
Aims The cancer stem cell concept proposes that tumor growth and recurrence is driven by a small population of cancer stem cells (CSCs). In this study we investigated the expression of induced-pluripotent stem cell (iPSC) markers and their localization in primary low-grade adenocarcinoma (LGCA) and high-grade adenocarcinoma (HGCA) and their patient-matched normal colon samples. Materials and methods Transcription and translation of iPSC markers OCT4, SOX2, NANOG, KLF4 and c-MYC were investigated using immunohistochemical (IHC) staining, RT-qPCR and in-situ hybridization (ISH). Results All five iPSC markers were detected at the transcriptional and translational levels. Protein abundance was found to be correlated with tumor grade. Based on their protein expression within the tumors, two sub-populations of cells were identified: a NANOG + /OCT4 - epithelial subpopulation and an OCT4 + /NANOG - stromal subpopulation. All cases were accurately graded based on four pieces of iPSC marker-related data. Conclusions This study suggests the presence of two putative sub-populations of CSCs: a NANOG + /OCT4 - epithelial subpopulation and an OCT4 + /NANOG - stromal subpopulation. Normal colon, LGCA and HGCA could be accurately distinguished from one another using iPSC marker expression. Once validated, novel combinations of iPSC markers may provide diagnostic and prognostic value to help guide patient management.
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