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

doi:10.1016/j.oraloncology.2010.11.011

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

107 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 language	English
Pages (from-to)	83-91
Number of pages	9
Journal	Oral Oncology
Volume	47
Issue number	2
DOIs	https://doi.org/10.1016/j.oraloncology.2010.11.011
Publication status	Published - 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.).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Head and neck neoplasms
Neoplastic stem cells
Oral cancer
Squamospheres

ASJC Scopus subject areas

Oral Surgery
Oncology
Cancer Research

Access to Document

10.1016/j.oraloncology.2010.11.011

Cite this

@article{845fc60e2cb84723965cf9ec35acda4a,

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 × 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.",

keywords = "Head and neck neoplasms, Neoplastic stem cells, Oral cancer, Squamospheres",

author = "Lim, \{Young Chang\} and Oh, \{Se Yeong\} and Cha, \{Yun Yi\} and Kim, \{Sung Hak\} and Xun Jin and Hyunggee Kim",

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.).",

year = "2011",

month = feb,

doi = "10.1016/j.oraloncology.2010.11.011",

language = "English",

volume = "47",

pages = "83--91",

journal = "Oral Oncology",

issn = "1368-8375",

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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

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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 -

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

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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