Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas

Young Chang Lim, Se Yeong Oh, Yun Yi Cha, Sung Hak Kim, Xun Jin, Hyunggee Kim

Research output: Contribution to journalArticlepeer-review

102 Citations (Scopus)

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 × 106 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.

Original languageEnglish
Pages (from-to)83-91
Number of pages9
JournalOral Oncology
Volume47
Issue number2
DOIs
Publication statusPublished - 2011 Feb

Bibliographical note

Funding Information:
We would like to thank Dr. Se-Hyuk Kim (Ajou University College of Medicine) for his technical advice on stem cell suspension culture conditions. We thank all members of the Cell Growth Regulation Laboratory for their critical input and suggestions. This work is supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2010-0022256 to Y.C.L. and 2008-0058785 to H.K.).

Keywords

  • Head and neck neoplasms
  • Neoplastic stem cells
  • Oral cancer
  • Squamospheres

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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