title: Cancer stem cells maintain a hierarchy of differentiation by creating their niche.
abstract: 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.
authors: Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan.
authors: Shuichi
authors: S
authors: Matsuda
authors: Ting
authors: T
authors: Yan
authors: Akifumi
authors: A
authors: Mizutani
authors: Tatsuyuki
authors: T
authors: Sota
authors: Yuki
authors: Y
authors: Hiramoto
authors: Marta
authors: M
authors: Prieto-Vila
authors: Ling
authors: L
authors: Chen
authors: Ayano
authors: A
authors: Satoh
authors: Takayuki
authors: T
authors: Kudoh
authors: Tomonari
authors: T
authors: Kasai
authors: Hiroshi
authors: H
authors: Murakami
authors: Li
authors: L
authors: Fu
authors: David S
authors: DS
authors: Salomon
authors: Masaharu
authors: M
authors: Seno
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology*; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics
keywords: cancer stem cell; differentiation; niche; self-renewal; vascular endothelium