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A Gradual Rise in Cancer Stem Cells in the Crypt‐Villous Axis of the Colon During Aging
Author(s) -
Majumdar Adhip,
NangiaMakker Pratima,
Yu Yingjie
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1000.1
Subject(s) - colorectal cancer , cancer stem cell , stem cell , crypt , cd44 , bmi1 , malignancy , biology , pathology , cd24 , pathological , cancer research , cancer , medicine , cell , microbiology and biotechnology , endocrinology , genetics
One of the most consistent pathological conditions in the gastrointestinal (GI) tract with advancing age is malignancy, specifically colorectal cancer. Although the underlying cellular and molecular events are not fully understood, we have suggested a role for self‐renewing pluripotent cancer stem/stem‐like cells (CSCs) in this process. Earlier, we demonstrated that the age‐related increase in colonic polyps is associated with a concomitant rise in CSCs. An age‐related rise in CSCs in the colon is also observed in experimental animals. Since CSCs are thought to be the mutated counterpart of normal stem cells, we hypothesize that a gradual increase in CSCs in the crypt‐villous axis of the colon may lead to tumor. To test this hypothesis, we isolated mucosal cells from the upper, middle and lower regions of the colon of young and aged Fischer‐344 rats and subjected them to functional assays for CSCs and for mutational status. We found that mucosal cells from the middle and lower, but not the upper part of the colon formed spheres/spheroids, but was much higher in aged than young animals. This increased spheroid forming ability of mucosal cells from aged rats was also associated with increased expression of CD44 and b‐catenin. In contrast, CK‐20, a marker of differentiation, was augmented in the middle/upper part of aged colon, compared to lower region. In addition, spheres formed by mucosal cells from aged, but not young rats could be expanded to 2 nd generation, indicating higher self‐renewal ability of CSCs of aged rats. Frequency of gene mutation was also higher in the lower region of the colon of aged than young rats. We conclude that with aging there is a gradual increase in CSCs in the colonic crypt which may partly be responsible for the age‐related rise in colorectal cancer.