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Age-related increase in colorectal cancer stem cells in macroscopically normal mucosa of patients with adenomas: A risk factor for colon cancer
Authors:Bhaumik B Patel  Yingjie Yu  Jianhua Du  Edi Levi  Phillip A Phillip  Adhip PN Majumdar
Institution:1. Department of Clinical Sciences Malmö, Lund University, Sweden;2. Vascular Center, Skåne University Hospital, S-20502 Malmö;3. Department of Radiology, Skåne University Hospital, S-20502 Malmö;4. Department of Nephrology and Transplantation, Skåne University Hospital, S-20502 Malmö;1. Molecular NeuroImaging, LLC, New Haven, CT, USA;2. Institute for Neurodegenerative Disorders, New Haven, CT, USA;3. Yale University, New Haven, CT, USA
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 (r2 = 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.
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