TY - JOUR
T1 - Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas
AU - Lim, Young Chang
AU - Oh, Se Yeong
AU - Cha, Yun Yi
AU - Kim, Sung Hak
AU - Jin, Xun
AU - Kim, Hyunggee
N1 - 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.).
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - Head and neck neoplasms
KW - Neoplastic stem cells
KW - Oral cancer
KW - Squamospheres
UR - http://www.scopus.com/inward/record.url?scp=79551686424&partnerID=8YFLogxK
U2 - 10.1016/j.oraloncology.2010.11.011
DO - 10.1016/j.oraloncology.2010.11.011
M3 - Article
C2 - 21167769
AN - SCOPUS:79551686424
SN - 1368-8375
VL - 47
SP - 83
EP - 91
JO - Oral Oncology
JF - Oral Oncology
IS - 2
ER -