Non-small cell lung cancer stem/progenitor cells are enriched in multiple distinct phenotypic subpopulations and exhibit plasticity

• Published in: Cell death & disease 2012-07, Vol.3 (7), p.e352-e352
• Main Authors: Akunuru, S, James Zhai, Q, Zheng, Y
• Format: Article
• Language: English
• Subjects: 692/699/67/1612/1350; AC133 Antigen; Aldehyde Dehydrogenase - metabolism; Antibodies; Antigens, CD - metabolism; Apoptosis; Biochemistry; Biomedical and Life Sciences; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Biology; Cell Culture; Epithelial-Mesenchymal Transition - drug effects; Glycoproteins - metabolism; Humans; Immunology; Life Sciences; Lung cancer; Neoplastic Stem Cells - cytology; Neoplastic Stem Cells - metabolism; Original; original-article; Peptides - metabolism; Phenotype; rac1 GTP-Binding Protein - antagonists & inhibitors; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - metabolism; RNA Interference; RNA, Small Interfering - metabolism; Transforming Growth Factor beta1 - pharmacology; Tumor Cells, Cultured
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2012.93

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.