Abstract
AimsThe 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 methodsTranscription 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).ResultsAll 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.ConclusionsThis 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.
Highlights
The cancer stem cell (CSC) concept hypothesizes that tumor growth is driven by cancer stem cells (CSCs), a small subpopulation of cancer cells with stem cell characteristics [1,2,3,4]
This study suggests the presence of two putative sub-populations of CSCs: a NANOG+/ OCT4- epithelial subpopulation and an OCT4+/NANOG- stromal subpopulation
We investigated the level of induced-pluripotent stem cell (iPSC) marker transcription and translation, and their distribution within the epithelium and stroma, to determine the difference between low-grade colon adenocarcinoma (CA) (LGCA) and high-grade CA (LGCA) and their patient-matched normal colon (NC), using
Summary
The cancer stem cell (CSC) concept hypothesizes that tumor growth is driven by CSCs, a small subpopulation of cancer cells with stem cell characteristics [1,2,3,4]. CSCs produce identical daughter pluripotent cells, as well as progenitor cells which are more committed and sit on a hierarchy between CSCs and terminally differentiated cancer cells [5,6,7]. Cells within this hierarchy can be identified by their expression of different combinations of markers [6, 8]. Takahashi and Yamanaka [9] first used octamer-binding transcription factor 4 (OCT4, POU5F1), sex-determining region Y-box 2 (SOX2), Kruppel-like factor 4 (KLF4) and c-MYC to produce induced-pluripotent stem cells (iPSCs). The Thomson laboratory produced iPSCs from human fibroblasts using OCT4, SOX2, NANOG and LIN28 [10]
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