title: The side population in human lung cancer cell line NCI-H460 is enriched in stem-like cancer cells.
abstract: Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate. Recent studies indicate that tumors contain a subset of stem-like cancer cells that possess certain stem cell properties. Herein, we used Hoechst 33342 dye efflux assay and flow cytometry to isolate and characterize the side population (SP) cells from human lung cancer cell line NCI-H460 (H460). We show that the H460 SP cells harbor stem-like cells as they can readily form anchorage-independent floating spheres, possess great proliferative potential, and exhibit enhanced tumorigenicity. Importantly, the H460 SP cells were able to self-renew both in vitro and in vivo. Finally, we show that the H460 SP cells preferentially express ABCG2 as well as SMO, a critical mediator of the Hedgehog (HH) signaling, which seems to play an important role in H460 lung cancer cells as its blockage using Cyclopamine greatly inhibits cell-cycle progression. Collectively, our results lend further support to the existence of lung cancer stem cells and also implicate HH signaling in regulating large-cell lung cancer (stem) cells.
authors.affiliation: Department of Pathology, East Hospital, Tongji University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Xuelian
authors.initials: X
authors.lastname: Fu
authors.forename: Yong
authors.initials: Y
authors.lastname: Hua
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Junchen
authors.initials: J
authors.lastname: Wang
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000704:Analysis of Variance; D001562:Benzimidazoles; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058985:Side-Population Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D000072086:Smoothened Receptor; D014704:Veratrum Alkaloids
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001562:Benzimidazoles; D017931:DNA Primers; D005456:Fluorescent Dyes; D053823:Hedgehog Proteins; D009363:Neoplasm Proteins; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014704:Veratrum Alkaloids; C017807:bisbenzimide ethoxide trihydrochloride; C000541:cyclopamine