title: Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas.
abstract: A subpopulation of cancer stem cells (CSCs), but not the majority of non-tumorigenic cancer cells, in a variety of human malignancies plays a critical role in cancer cell proliferation, invasion, metastasis, and tumor recurrence post-therapies. We report the isolation of sphere-forming cells (squamospheres) from primary head and neck squamous cell carcinomas (HNSCCs), and characterization of their CSC properties. Squamospheres appeared within 2 weeks after seeding as single-dissociated cells obtained from primary HNSCC specimens in serum-free culture conditions. Real-time RT-PCR and immunocytochemistry assays revealed that a number of stem cell markers, including CK5, OCT4, SOX2, and nestin, were up-regulated in HNSCC-driven squamospheres. Fluorescence-activated cell sorting (FACS) analysis showed that squamospheres contain enriched side population cells compared to serum-induced differentiated squamosphere cells. Furthermore, HNSCC-driven squamospheres appeared to be chemoresistant to cisplatin, 5-fluorouracil (FU), paclitaxel and doxetaxel, and showed increased levels of ABCG2, one of the ATP-binding cassette (ABC) transporters. Of particular interest, in sharp contrast to subcutaneous injection of 1×10(6) differentiated squamosphere cells, as few as 100 squamosphere cells were able to give rise to tumors in nude mice. Altogether, we assert that primary HNSCC-driven squamospheres possess CSC properties, and its functional analysis may provide a novel tool for investigating the tumorigenic process of HNSCC.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Republic of Korea.
authors.forename: Young Chang
authors.initials: YC
authors.lastname: Lim
authors.forename: Se-Yeong
authors.initials: SY
authors.lastname: Oh
authors.forename: Yun Yi
authors.initials: YY
authors.lastname: Cha
authors.forename: Sung-Hak
authors.initials: SH
authors.lastname: Kim
authors.forename: Xun
authors.initials: X
authors.lastname: Jin
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000378:metabolism* / Q000473:pathology; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D005472:Fluorouracil