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01-07-2012 | Translational Research and Biomarkers

Increased CD13 Expression Reduces Reactive Oxygen Species, Promoting Survival of Liver Cancer Stem Cells via an Epithelial–Mesenchymal Transition-like Phenomenon

Authors: Ho Min Kim, Naotsugu Haraguchi, Hideshi Ishii, Masahisa Ohkuma, Miho Okano, Koshi Mimori, Hidetoshi Eguchi, Hirofumi Yamamoto, Hiroaki Nagano, Mitsugu Sekimoto, Yuichiro Doki, Masaki Mori

Published in: Annals of Surgical Oncology | Special Issue 3/2012

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.

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).

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.

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.

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Title: Increased CD13 Expression Reduces Reactive Oxygen Species, Promoting Survival of Liver Cancer Stem Cells via an Epithelial–Mesenchymal Transition-like Phenomenon
Authors: Ho Min Kim
Naotsugu Haraguchi
Hideshi Ishii
Masahisa Ohkuma
Miho Okano
Koshi Mimori
Hidetoshi Eguchi
Hirofumi Yamamoto
Hiroaki Nagano
Mitsugu Sekimoto
Yuichiro Doki
Masaki Mori
Publication date: 01-07-2012
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue Special Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-011-2040-5

Keynote webinar | Spotlight on medication adherence

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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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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