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Increased CD13 expression reduces reactive oxygen species, promoting survival of liver cancer stem cells via an epithelial-mesenchymal transition-like phenomenon.
- Source :
-
Annals of surgical oncology [Ann Surg Oncol] 2012 Jul; Vol. 19 Suppl 3, pp. S539-48. Date of Electronic Publication: 2011 Aug 31. - Publication Year :
- 2012
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Abstract
- Background: Recently, it has been reported that a small population of cancer stem cells (CSCs) play a role in resistance to chemotherapy and radiation therapy. We reported that CD13(+) liver CSCs survive in hypoxic lesions after chemotherapy, presumably through increased expression of CD13/Aminopeptidase N, which is a scavenger enzyme in the reactive oxygen species (ROS) metabolic pathway. On the other hand, the concept of epithelial-mesenchymal transition (EMT) was indicated by a recent study showing an increased plasticity linked to the cellular "stemness" of CSCs.<br />Methods: To study the relationship between CSCs and EMT, we examined biological characteristics of liver cancer cell lines with EMT by exposing transforming growth factor-β (TGF-β).<br />Results: We showed that a TGF-β-induced EMT-like phenomenon is associated with increased CD13 expression in liver cancer cells. This phenomenon prevents further increases in the ROS level as well as the induction of apoptosis, promoting the survival of CD13(+) CSCs, whereas inhibition of CD13 stimulates apoptosis. Immunohistochemical analysis also indicated that after chemotherapy, CD13 was coexpressed with N-cadherin in surviving cancer cells within fibrous capsules. We have demonstrated that CD13 expression plays a role in supporting the survival of CSCs and that there is an EMT-associated reduction in ROS elevation.<br />Conclusions: This novel and consistent linkage between functional CSC markers and the EMT phenomenon suggests a bona fide candidate for targeted therapy for EMT-mediated invasion and metastasis of liver cancer.
- Subjects :
- Apoptosis
CD13 Antigens drug effects
CD13 Antigens genetics
Cadherins metabolism
Carcinoma, Hepatocellular drug therapy
Carcinoma, Hepatocellular genetics
Cell Line, Tumor
Chi-Square Distribution
Drug Resistance, Neoplasm
Gene Expression
Humans
Liver Neoplasms drug therapy
Liver Neoplasms genetics
Polycomb Repressive Complex 1 metabolism
RNA, Messenger metabolism
Receptor, Notch1 metabolism
Statistics, Nonparametric
Transforming Growth Factor beta pharmacology
Tumor Stem Cell Assay
CD13 Antigens metabolism
Carcinoma, Hepatocellular metabolism
Epithelial-Mesenchymal Transition drug effects
Liver Neoplasms metabolism
Neoplastic Stem Cells metabolism
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1534-4681
- Volume :
- 19 Suppl 3
- Database :
- MEDLINE
- Journal :
- Annals of surgical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 21879266
- Full Text :
- https://doi.org/10.1245/s10434-011-2040-5