TY - JOUR
T1 - Roles of the hypoxia response system in hematopoietic and leukemic stem cells
AU - Takubo, Keiyo
AU - Suda, Toshio
N1 - Funding Information:
Acknowledgments We would like to thank Drs. Atsushi Hirao, Makoto Suematsu, Nobuhito Goda, Tomoyoshi Soga, Eiji Ikeda, and Randall S. Johnson for providing thoughtful insights and collaborations for this review. We would like to acknowledge our deep appreciation of fruitful discussions with the previous and current members of the Stem Cell Metabolism group of the Suda lab, especially Dr. Hirono Iriuchishima, Dr. Chiharu Kobayashi, Dr. June-Won Cheong, Dr. Ayako Ishizu, Dr. Hiroshi Kobayashi, and Ms. Wakako Yamada. Furthermore, we would like to thank Ms. Tomoko Muraki, Ms. Ayako Kumakubo and Ms. Takako Hirose for the preparation of this manuscript. K.T. is supported by the Global COE Program for Human Metabolomic Systems Biology and for Stem Cell Medicine of the Japan Society for Promotion of Science, and also in part by a Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for Young Scientists (A) and a MEXT Grant-in-Aid for Scientific Research on Innovative Areas. T.S. was supported in part by a MEXT Grant-in-Aid for Scientific Research (A) and a MEXT Grant-in-Aid for Scientific Research on Innovative Areas.
PY - 2012/5
Y1 - 2012/5
N2 - Stem cells exhibit a number of characteristic features, including the capacity for self-renewal and differentiation into multiple cell types, stress resistance, and drug efflux activity. These specific biological characteristics are supported by signals from the surrounding niche and the stemcell-specific transcription factor set, including hypoxia and the machinery that senses low oxygen levels. These properties are essential for normal stem cells, and when defective may induce cellular senescence and tumorigenesis. In contrast, cancer stem cells in tumor tissue utilize these biological characters driven by stemcell-specific molecular mechanisms and acquire indefinite selfrenewal capacity, drug resistance, and metastatic ability. A fuller understanding of the differences between normal and malignant stem cells in the biological and molecular context is, therefore, necessary to the development of therapies against cancer stem cells. In this review, we discuss the effect of hypoxic microenvironment on normal and malignant stem cells and describe their molecular machinery with an emphasis on hematopoietic stem cells and their malignant counterparts, leukemic stem cells.
AB - Stem cells exhibit a number of characteristic features, including the capacity for self-renewal and differentiation into multiple cell types, stress resistance, and drug efflux activity. These specific biological characteristics are supported by signals from the surrounding niche and the stemcell-specific transcription factor set, including hypoxia and the machinery that senses low oxygen levels. These properties are essential for normal stem cells, and when defective may induce cellular senescence and tumorigenesis. In contrast, cancer stem cells in tumor tissue utilize these biological characters driven by stemcell-specific molecular mechanisms and acquire indefinite selfrenewal capacity, drug resistance, and metastatic ability. A fuller understanding of the differences between normal and malignant stem cells in the biological and molecular context is, therefore, necessary to the development of therapies against cancer stem cells. In this review, we discuss the effect of hypoxic microenvironment on normal and malignant stem cells and describe their molecular machinery with an emphasis on hematopoietic stem cells and their malignant counterparts, leukemic stem cells.
KW - Hematopoietic stem cell
KW - Hypoxia
KW - Leukemic stem cell
KW - Stem cell niche
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U2 - 10.1007/s12185-012-1071-4
DO - 10.1007/s12185-012-1071-4
M3 - Article
C2 - 22539363
AN - SCOPUS:84862894073
SN - 0925-5710
VL - 95
SP - 478
EP - 483
JO - International journal of hematology
JF - International journal of hematology
IS - 5
ER -
