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Cancer Stem Cells in the Age‐related Progression of Colorectal Cancer: Role of EGFR
Author(s) -
Majumdar Adhip P.N.,
Leavell Bonita,
Du Jianhua,
Yang Liu,
Antaki Fadi
Publication year - 2012
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.26.1_supplement.1161.1
Subject(s) - colorectal cancer , cd44 , malignancy , cancer stem cell , cancer , medicine , cancer research , pathological , oncology , pathology , biology , cell , genetics
One of the most consistent pathological conditions in the gastrointestinal (GI) tract with advancing age is malignancy, particularly colorectal cancer, the incidence of which increases sharply with advancing age. The regulatory mechanisms are poorly understood. Recent evidence suggests that colorectal cancer is driven by self‐renewing cancer stem cells (CSCs). Earlier, we reported that the age‐related increase in adenomas was associated with increased expression of CSC markers in the macroscopically normal mucosa suggesting a role for CSCs in the development of colorectal neoplasia. Indeed, FACS analysis of cells isolated from colonic biopsies of patients with adenomas over 60 years of age revealed a higher proportion of colonocytes expressing CD44+166− and CD44+CD166+ phenotypes than their younger counterparts. This was accompanied by a concomitant increase in EGFR in the colonic mucosa, indicating a relationship between CSCs and EGFR. Moreover, we found EGFR to be coexpressed with CD166 in the colonic crypts and that their co‐expression was significantly higher in older patients. This co‐expression was even more evident in adenomas and highest in carcinomas. In conclusion, our data suggest that EGFR plays a pivotal role in the age‐related increase in CSCs which may promote their carcinogenic potential.