Age-related increase in colorectal cancer stem cells in macroscopically normal mucosa of patients with adenomas: a risk factor for colon cancer.
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.
Patel
Bhaumik B
BB
Veterans Administration Medical Center, Wayne State University, Detroit, Michigan 48201, USA.
Yu
Yingjie
Y
Du
Jianhua
J
Levi
Edi
E
Phillip
Phillip A
PA
Majumdar
Adhip P N
AP
D018256:Adenomatous Polyps / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D015703:Antigens, CD / Q000032:analysis; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis; D003110:Colonic Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology*; D005326:Fetal Proteins / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D015994:Incidence; D007413:Intestinal Mucosa / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D020410:Activated-Leukocyte Cell Adhesion Molecule
D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D018960:Hyaluronan Receptors; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule