Cancer stem cell subpopulations in primary colon adenocarcinoma

PLoS One. 2019 Sep 6;14(9):e0221963. doi: 10.1371/journal.pone.0221963. eCollection 2019.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Biomarkers, Tumor / metabolism
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Factor 4
  • Neoplasm Grading
  • Neoplastic Stem Cells / pathology*

Substances

  • Biomarkers, Tumor
  • KLF4 protein, human
  • Kruppel-Like Factor 4

Grants and funding

MM was supported by a scholarship from the New Zealand Community Trust, 75841. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.