Age-related increase in colorectal cancer stem cells in macroscopically normal mucosa of patients with adenomas: a risk factor for colon cancer

Biochem Biophys Res Commun. 2009 Jan 16;378(3):344-7. doi: 10.1016/j.bbrc.2008.10.179. Epub 2008 Nov 14.

Abstract

It is becoming increasingly evident that cancer stem cells play a vital role in development and progression of cancers and relapse following chemotherapy. The present study examines the presence of cancer stem-like cells (CSC) in adenomatous polyps and in normal appearing colonic mucosa in humans during aging. The number of polyps was found to increase linearly with advancing age (r(2)=0.92, p<0.02). Immunohistochemical analysis revealed co-localization of CSC markers CD44 and CD166 in colonic polyps. Real-time RT-PCR analysis of normal appearing mucosa from subjects with adenomatous polyps showed an age-related rise in CSC as evidenced by the increased expression of CD44, CD166 and ESA. A similar phenomenon was also observed for EGFR. In addition, the expression each CSC marker was found to be about 2-fold higher in subjects with 3-4 polyps than those with 1-2 polyps. In conclusion, our results show that colon cancer stem-like cells are present in the premalignant adenomatous polyps as well in normal appearing colonic mucosa. Moreover, our observation of the age-related rise in CSC in macroscopically normal colonic mucosa suggests a predisposition of the organ to developing colorectal cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenomatous Polyps / epidemiology*
  • Adenomatous Polyps / etiology
  • Adenomatous Polyps / pathology*
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / pathology
  • Antigens, CD / analysis
  • Cell Adhesion Molecules, Neuronal / analysis
  • Colonic Neoplasms / epidemiology*
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / pathology*
  • Fetal Proteins / analysis
  • Humans
  • Hyaluronan Receptors / analysis
  • Incidence
  • Intestinal Mucosa / pathology*
  • Neoplastic Stem Cells / pathology*
  • Risk Factors
  • United States / epidemiology

Substances

  • ALCAM protein, human
  • Antigens, CD
  • Cell Adhesion Molecules, Neuronal
  • Fetal Proteins
  • Hyaluronan Receptors