title: Non-small cell lung cancer stem/progenitor cells are enriched in multiple distinct phenotypic subpopulations and exhibit plasticity.
abstract: Cancer stem cells (CSCs) represent a population of cancer cells that possess unique self-renewal and differentiation characteristics required for tumorigenesis and are resistant to chemotherapy-induced apoptosis. Lung CSCs can be enriched by several markers including drug-resistant side population (SP), CD133(pos) and ALDH(high). Using human non-small cell lung adenocarcinoma cell lines and patient-derived primary tumor cells, we demonstrate that SP cells represent a subpopulation distinct from other cancer stem/progenitor cell (CS/PC) populations marked by CD133(pos) or ALDH(high). The non-CS/PCs and CS/PCs of each subpopulation are interconvertible. Epithelial-mesenchymal transition (EMT) promotes the formation of CD133(pos) and ALDH(high) CS/PC subpopulations while suppressing the SP CS/PC subpopulation. Rac1 GTPase activity is significantly increased in cells that have undergone EMT, and targeting Rac1 is effective in inhibiting the dynamic conversion of non-CS/PCs to CS/PCs, as well as the CS/PC activity. These results imply that various subpopulations of CS/PCs and non-CS/PCs may achieve a stochastic equilibrium in a defined microenvironment, and eliminating multiple subpopulations of CS/PCs and effectively blocking non-CS/PC to CS/PC transition, by an approach such as targeting Rac1, can be a more effective therapy.
authors: Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors: S
authors: S
authors: Akunuru
authors: Q
authors: Q
authors: James Zhai
authors: Y
authors: Y
authors: Zheng
mesh_terms: D000071916:AC133 Antigen; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D000444:Aldehyde Dehydrogenase; D020830:rac1 GTP-Binding Protein