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 language | English |
|---|---|
| Pages (from-to) | 83-91 |
| Number of pages | 9 |
| Journal | Oral Oncology |
| Volume | 47 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2011 Feb 1 |
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Keywords
- Head and neck neoplasms
- Neoplastic stem cells
- Oral cancer
- Squamospheres
ASJC Scopus subject areas
- Oncology
- Oral Surgery
- Cancer Research
Cite this
Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas. / Lim, Young Chang; Oh, Se Yeong; Cha, Yun Yi; Kim, Sung Hak; Jin, Xun; Kim, Hyunggee.
In: Oral Oncology, Vol. 47, No. 2, 01.02.2011, p. 83-91.Research output: Contribution to journal › Article
}
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
PY - 2011/2/1
Y1 - 2011/2/1
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
UR - http://www.scopus.com/inward/citedby.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
VL - 47
SP - 83
EP - 91
JO - Oral Oncology
JF - Oral Oncology
SN - 1368-8375
IS - 2
ER -