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Cancer stem cells maintain a hierarchy of differentiation by creating their niche
Author(s) -
Matsuda Shuichi,
Yan Ting,
Mizutani Akifumi,
Sota Tatsuyuki,
Hiramoto Yuki,
PrietoVila Marta,
Chen Ling,
Satoh Ayano,
Kudoh Takayuki,
Kasai Tomonari,
Murakami Hiroshi,
Fu Li,
Salomon David S.,
Seno Masaharu
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28648
Subject(s) - microbiology and biotechnology , stem cell , cancer stem cell , biology , cellular differentiation , niche , notch signaling pathway , in vitro , cancer research , signal transduction , genetics , biochemistry , gene
The self‐renewal and differentiation properties of cancer stem cells (CSCs) are regulated and maintained by the CSC niche. However, the mechanism of this maintenance, especially the maintenance contributed by differentiated cancer cells, remains to be fully elucidated. Recently, we have established a model of CSCs, miPS‐LLCcm, from mouse induced pluripotent stem cells (miPSCs). In vitro cultured miPS‐LLCcm cells were autonomously balanced with stem‐like cells and differentiated cells including vascular endothelial cells. Under these conditions, the CSC properties appeared to be stable in the presence of the factor(s) secreted by the differentiated cells. The factor(s) activated Notch signaling and promoted self‐renewal of CSCs. In addition, the secreted factor(s) appeared to regulate the differentiation lineage of CSCs. Our results indicate that the differentiated progenies of CSCs containing vascular endothelium play important roles for regulating the CSC's properties. Therefore, miPS‐LLCcm cells create their own in vitro niche to maintain themselves in the hierarchy of differentiating CSCs.