Cancer stem cells are enriched in the side population cells in a mouse model of glioma

Molly A Harris; Hyuna Yang; Benjamin E Low; Joydeep Mukherjee; Joydeep Mukherje; Abhijit Guha; Roderick T Bronson; Leonard D Shultz; Mark A Israel; Kyuson Yun

doi:10.1158/0008-5472.CAN-08-0786

Cancer stem cells are enriched in the side population cells in a mouse model of glioma

Molly A Harris, Hyuna Yang, Benjamin E Low, Joydeep Mukherjee, Joydeep Mukherje, Abhijit Guha, Roderick T Bronson, Leonard D Shultz, Mark A Israel, Kyuson Yun

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

131 Scopus citations

Abstract

The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100beta-verbB;Trp53. In this glioma model, CSCs are enriched in the side population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared with non-SP cells from the same tumors. Furthermore, gene expression analysis comparing fluorescence-activated cell sorting-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human glioblastoma multiforme cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the CSC hypothesis.

Original language	English (US)
Pages (from-to)	10051-9
Number of pages	9
Journal	Cancer research
Volume	68
Issue number	24
DOIs	https://doi.org/10.1158/0008-5472.CAN-08-0786
State	Published - Dec 15 2008

Keywords

Animals
Brain Neoplasms
Cell Cycle Proteins
Gene Expression Profiling
Glioblastoma
Glioma
Humans
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Models, Animal
Neoplastic Stem Cells
Nerve Growth Factors
S100 Calcium Binding Protein beta Subunit
S100 Proteins
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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10.1158/0008-5472.CAN-08-0786

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@article{19fe7edd50a2477ca64d457cb8bcea33,

title = "Cancer stem cells are enriched in the side population cells in a mouse model of glioma",

abstract = "The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100beta-verbB;Trp53. In this glioma model, CSCs are enriched in the side population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared with non-SP cells from the same tumors. Furthermore, gene expression analysis comparing fluorescence-activated cell sorting-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human glioblastoma multiforme cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the CSC hypothesis.",

keywords = "Animals, Brain Neoplasms, Cell Cycle Proteins, Gene Expression Profiling, Glioblastoma, Glioma, Humans, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Models, Animal, Neoplastic Stem Cells, Nerve Growth Factors, S100 Calcium Binding Protein beta Subunit, S100 Proteins, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",

author = "Harris, {Molly A} and Hyuna Yang and Low, {Benjamin E} and Joydeep Mukherjee and Joydeep Mukherje and Abhijit Guha and Bronson, {Roderick T} and Shultz, {Leonard D} and Israel, {Mark A} and Kyuson Yun",

year = "2008",

month = dec,

day = "15",

doi = "10.1158/0008-5472.CAN-08-0786",

language = "English (US)",

volume = "68",

pages = "10051--9",

journal = "Cancer research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "24",

}

TY - JOUR

T1 - Cancer stem cells are enriched in the side population cells in a mouse model of glioma

AU - Harris, Molly A

AU - Yang, Hyuna

AU - Low, Benjamin E

AU - Mukherjee, Joydeep

AU - Mukherje, Joydeep

AU - Guha, Abhijit

AU - Bronson, Roderick T

AU - Shultz, Leonard D

AU - Israel, Mark A

AU - Yun, Kyuson

PY - 2008/12/15

Y1 - 2008/12/15

N2 - The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100beta-verbB;Trp53. In this glioma model, CSCs are enriched in the side population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared with non-SP cells from the same tumors. Furthermore, gene expression analysis comparing fluorescence-activated cell sorting-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human glioblastoma multiforme cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the CSC hypothesis.

AB - The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100beta-verbB;Trp53. In this glioma model, CSCs are enriched in the side population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared with non-SP cells from the same tumors. Furthermore, gene expression analysis comparing fluorescence-activated cell sorting-sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human glioblastoma multiforme cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the CSC hypothesis.

KW - Animals

KW - Brain Neoplasms

KW - Cell Cycle Proteins

KW - Gene Expression Profiling

KW - Glioblastoma

KW - Glioma

KW - Humans

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Inbred NOD

KW - Mice, SCID

KW - Mice, Transgenic

KW - Models, Animal

KW - Neoplastic Stem Cells

KW - Nerve Growth Factors

KW - S100 Calcium Binding Protein beta Subunit

KW - S100 Proteins

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1158/0008-5472.CAN-08-0786

DO - 10.1158/0008-5472.CAN-08-0786

M3 - Article

C2 - 19074870

SN - 0008-5472

VL - 68

SP - 10051

EP - 10059

JO - Cancer research

JF - Cancer research

IS - 24

ER -

Cancer stem cells are enriched in the side population cells in a mouse model of glioma

Abstract

Keywords

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