Expansion and characterization of cancer stem-like cells in squamous cell carcinoma of the head and neck.
Evidence has accumulated indicating that only a minority of cancer cells with stem cell properties, cancer stem cells (CSCs), are responsible for maintenance and growth of the tumor. CD44 is currently used to identify CSCs as one of the cell surface markers for solid tumors. Here we report the identification, expansion, and characterization of CD44+ cancer stem-like cells from a permanent squamous cell carcinoma of the head and neck (SCCHN) cell line. Under serum-free medium culture conditions, a small population (less than 3%) of CD44+ cells in a permanent cancer cell line was dramatically increased up to around 40%. The CD44+ cell population also showed higher expression of CD133 and ABCG2 as compared with the CD44- cell population. Moreover, CD44+ cells possess not only a marked capacity for forming tumor spheres, proliferation, migration, and invasion in vitro, but also resistance to chemotherapeutic agents. Four genes related to chemoresistance, ABCB1, ABCG2, CYP2C8, and TERT, were up-regulated in a CD44+ cell population. Our findings indicate that a subpopulation of CSCs is maintained in the SCCHN cell line, and the presence of such CSCs has an important clinical implication for head and neck cancer treatment. Further characterization of CSCs may provide new insights for novel therapeutic targets and prognostic markers.
Okamoto
Atsushi
A
Department of Otolaryngology-Head and Neck Surgery, University of Yamanashi, Faculty of Medicine, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
Chikamatsu
Kazuaki
K
Sakakura
Koichi
K
Hatsushika
Kyosuke
K
Takahashi
Goro
G
Masuyama
Keisuke
K
D000071916:AC133 Antigen; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D015703:Antigens, CD / Q000096:biosynthesis; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D016895:Culture Media, Serum-Free; D065727:Cytochrome P-450 CYP2C8; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007012:Hypopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D010455:Peptides; D019098:Telomerase / Q000096:biosynthesis
C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D016895:Culture Media, Serum-Free; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; C509186:TERT protein, human; D019098:Telomerase