Cancer stem cells: distinct entities or dynamically regulated phenotypes?
The origins of tumor-propagating neoplastic stem-like cells [cancer stem cells (CSC)] and their relationship to the bulk population of tumor cells that lack stem-like tumor-propagating features (i.e., transit-amplifying cancer progenitor cells) remain unclear. Recent findings from multiple laboratories show that cancer progenitor cells have the capacity to dedifferentiate and acquire a stem-like phenotype in response to either genetic manipulation or environmental cues. These findings suggest that CSCs and relatively differentiated progenitors coexist in dynamic equilibrium and are subject to bidirectional conversion. In this review, we discuss emerging concepts regarding the stem-like phenotype, its acquisition by cancer progenitor cells, and the molecular mechanisms involved. Understanding the dynamic equilibrium between CSCs and cancer progenitor cells is critical for the development of therapeutic strategies to deplete tumors of their tumor-propagating and treatment-resistant cell subpopulations.
Hugo W Moser Research Institute at Kennedy Krieger, and Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA. liyu@kennedykrieger.org
Yunqing
Y
Li
John
J
Laterra
D000818:Animals; D054337:Cell Dedifferentiation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics
D014157:Transcription Factors