A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma

Ruihuan Chen; Merry C. Nishimura; Stephanie M. Bumbaca; Samir Kharbanda; William F. Forrest; Ian M. Kasman; Joan M. Greve; Robert H. Soriano; Laurie L. Gilmour; Celina Sanchez Rivers; Zora Modrusan; Serban Nacu; Steve Guerrero; Kyle A. Edgar; Jeffrey J. Wallin; Katrin Lamszus; Manfred Westphal; Susanne Heim; C. David James; Scott R. VandenBerg; Joseph F. Costello; Scott Moorefield; Cynthia J. Cowdrey; Michael Prados; Heidi S. Phillips

doi:10.1016/j.ccr.2009.12.049

A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma

Ruihuan Chen, Merry C. Nishimura, Stephanie M. Bumbaca, Samir Kharbanda, William F. Forrest, Ian M. Kasman, Joan M. Greve, Robert H. Soriano, Laurie L. Gilmour, Celina Sanchez Rivers, Zora Modrusan, Serban Nacu, Steve Guerrero, Kyle A. Edgar, Jeffrey J. Wallin, Katrin Lamszus, Manfred Westphal, Susanne Heim, C. David James, Scott R. VandenBergJoseph F. Costello, Scott Moorefield, Cynthia J. Cowdrey, Michael Prados, Heidi S. Phillips^*

^*Corresponding author for this work

Neurological Surgery

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

465 Scopus citations

Abstract

The neural stem cell marker CD133 is reported to identify cells within glioblastoma (GBM) that can initiate neurosphere growth and tumor formation; however, instances of CD133^- cells exhibiting similar properties have also been reported. Here, we show that some PTEN-deficient GBM tumors produce a series of CD133⁺ and CD133^- self-renewing tumor-initiating cell types and provide evidence that these cell types constitute a lineage hierarchy. Our results show that the capacities for self-renewal and tumor initiation in GBM need not be restricted to a uniform population of stemlike cells, but can be shared by a lineage of self-renewing cell types expressing a range of markers of forebrain lineage.

Original language	English (US)
Pages (from-to)	362-375
Number of pages	14
Journal	Cancer cell
Volume	17
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2009.12.049
State	Published - Apr 13 2010

Funding

We thank M. Baatz and J. Zimmermann for implementation of the image analysis solution; J. Eastham-Anderson and J. Zha for assistance with histological analysis; T. Le, W. Tombo, and J. Ayers for expert technical assistance; J. Cupp for FACS consultation; A. Bruce for graphics; T. Wu for bioinformatics support; and G. Plowman for helpful discussions. This study was supported by the State of California and the University of California Industry-University Cooperative Research Discovery (grant Bio05-10501), the National Brain Tumor Society (support to J.F.C. and S.M.), and by the National Institutes of Health (grant CA 097257 to C.D.J., S.R.V., and M.D.P.). R.C., M.C.N., S.M.B., S.K., W.F.F., I.M.K., J.M.G., R.H.S., L.L.G., C.S.R., Z.M., S.N., S.G., K.A.E., J.J.W., and H.S.P. are employees of Genentech, Inc., a member of the Roche group. This work was supported in part by a grant from Genentech to C.D.J., S.R.V., J.F.C., S.M., M.P., and C.C. M.P. has received research grant support from Genentech for clinical trials that were not related in any way with the research described in this manuscript.

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccr.2009.12.049

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Chen, R., Nishimura, M. C., Bumbaca, S. M., Kharbanda, S., Forrest, W. F., Kasman, I. M., Greve, J. M., Soriano, R. H., Gilmour, L. L., Rivers, C. S., Modrusan, Z., Nacu, S., Guerrero, S., Edgar, K. A., Wallin, J. J., Lamszus, K., Westphal, M., Heim, S., James, C. D., ... Phillips, H. S. (2010). A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma. Cancer cell, 17(4), 362-375. https://doi.org/10.1016/j.ccr.2009.12.049

@article{34ed24e3c16a4ca793750e414ecb0288,

title = "A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma",

abstract = "The neural stem cell marker CD133 is reported to identify cells within glioblastoma (GBM) that can initiate neurosphere growth and tumor formation; however, instances of CD133- cells exhibiting similar properties have also been reported. Here, we show that some PTEN-deficient GBM tumors produce a series of CD133+ and CD133- self-renewing tumor-initiating cell types and provide evidence that these cell types constitute a lineage hierarchy. Our results show that the capacities for self-renewal and tumor initiation in GBM need not be restricted to a uniform population of stemlike cells, but can be shared by a lineage of self-renewing cell types expressing a range of markers of forebrain lineage.",

keywords = "CELLCYCLE",

author = "Ruihuan Chen and Nishimura, {Merry C.} and Bumbaca, {Stephanie M.} and Samir Kharbanda and Forrest, {William F.} and Kasman, {Ian M.} and Greve, {Joan M.} and Soriano, {Robert H.} and Gilmour, {Laurie L.} and Rivers, {Celina Sanchez} and Zora Modrusan and Serban Nacu and Steve Guerrero and Edgar, {Kyle A.} and Wallin, {Jeffrey J.} and Katrin Lamszus and Manfred Westphal and Susanne Heim and James, {C. David} and VandenBerg, {Scott R.} and Costello, {Joseph F.} and Scott Moorefield and Cowdrey, {Cynthia J.} and Michael Prados and Phillips, {Heidi S.}",

note = "Funding Information: We thank M. Baatz and J. Zimmermann for implementation of the image analysis solution; J. Eastham-Anderson and J. Zha for assistance with histological analysis; T. Le, W. Tombo, and J. Ayers for expert technical assistance; J. Cupp for FACS consultation; A. Bruce for graphics; T. Wu for bioinformatics support; and G. Plowman for helpful discussions. This study was supported by the State of California and the University of California Industry-University Cooperative Research Discovery (grant Bio05-10501), the National Brain Tumor Society (support to J.F.C. and S.M.), and by the National Institutes of Health (grant CA 097257 to C.D.J., S.R.V., and M.D.P.). R.C., M.C.N., S.M.B., S.K., W.F.F., I.M.K., J.M.G., R.H.S., L.L.G., C.S.R., Z.M., S.N., S.G., K.A.E., J.J.W., and H.S.P. are employees of Genentech, Inc., a member of the Roche group. This work was supported in part by a grant from Genentech to C.D.J., S.R.V., J.F.C., S.M., M.P., and C.C. M.P. has received research grant support from Genentech for clinical trials that were not related in any way with the research described in this manuscript. ",

year = "2010",

month = apr,

day = "13",

doi = "10.1016/j.ccr.2009.12.049",

language = "English (US)",

volume = "17",

pages = "362--375",

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Chen, R, Nishimura, MC, Bumbaca, SM, Kharbanda, S, Forrest, WF, Kasman, IM, Greve, JM, Soriano, RH, Gilmour, LL, Rivers, CS, Modrusan, Z, Nacu, S, Guerrero, S, Edgar, KA, Wallin, JJ, Lamszus, K, Westphal, M, Heim, S, James, CD, VandenBerg, SR, Costello, JF, Moorefield, S, Cowdrey, CJ, Prados, M & Phillips, HS 2010, 'A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma', Cancer cell, vol. 17, no. 4, pp. 362-375. https://doi.org/10.1016/j.ccr.2009.12.049

TY - JOUR

T1 - A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma

AU - Chen, Ruihuan

AU - Nishimura, Merry C.

AU - Bumbaca, Stephanie M.

AU - Kharbanda, Samir

AU - Forrest, William F.

AU - Kasman, Ian M.

AU - Greve, Joan M.

AU - Soriano, Robert H.

AU - Gilmour, Laurie L.

AU - Rivers, Celina Sanchez

AU - Modrusan, Zora

AU - Nacu, Serban

AU - Guerrero, Steve

AU - Edgar, Kyle A.

AU - Wallin, Jeffrey J.

AU - Lamszus, Katrin

AU - Westphal, Manfred

AU - Heim, Susanne

AU - James, C. David

AU - VandenBerg, Scott R.

AU - Costello, Joseph F.

AU - Moorefield, Scott

AU - Cowdrey, Cynthia J.

AU - Prados, Michael

AU - Phillips, Heidi S.

N1 - Funding Information: We thank M. Baatz and J. Zimmermann for implementation of the image analysis solution; J. Eastham-Anderson and J. Zha for assistance with histological analysis; T. Le, W. Tombo, and J. Ayers for expert technical assistance; J. Cupp for FACS consultation; A. Bruce for graphics; T. Wu for bioinformatics support; and G. Plowman for helpful discussions. This study was supported by the State of California and the University of California Industry-University Cooperative Research Discovery (grant Bio05-10501), the National Brain Tumor Society (support to J.F.C. and S.M.), and by the National Institutes of Health (grant CA 097257 to C.D.J., S.R.V., and M.D.P.). R.C., M.C.N., S.M.B., S.K., W.F.F., I.M.K., J.M.G., R.H.S., L.L.G., C.S.R., Z.M., S.N., S.G., K.A.E., J.J.W., and H.S.P. are employees of Genentech, Inc., a member of the Roche group. This work was supported in part by a grant from Genentech to C.D.J., S.R.V., J.F.C., S.M., M.P., and C.C. M.P. has received research grant support from Genentech for clinical trials that were not related in any way with the research described in this manuscript.

PY - 2010/4/13

Y1 - 2010/4/13

N2 - The neural stem cell marker CD133 is reported to identify cells within glioblastoma (GBM) that can initiate neurosphere growth and tumor formation; however, instances of CD133- cells exhibiting similar properties have also been reported. Here, we show that some PTEN-deficient GBM tumors produce a series of CD133+ and CD133- self-renewing tumor-initiating cell types and provide evidence that these cell types constitute a lineage hierarchy. Our results show that the capacities for self-renewal and tumor initiation in GBM need not be restricted to a uniform population of stemlike cells, but can be shared by a lineage of self-renewing cell types expressing a range of markers of forebrain lineage.

AB - The neural stem cell marker CD133 is reported to identify cells within glioblastoma (GBM) that can initiate neurosphere growth and tumor formation; however, instances of CD133- cells exhibiting similar properties have also been reported. Here, we show that some PTEN-deficient GBM tumors produce a series of CD133+ and CD133- self-renewing tumor-initiating cell types and provide evidence that these cell types constitute a lineage hierarchy. Our results show that the capacities for self-renewal and tumor initiation in GBM need not be restricted to a uniform population of stemlike cells, but can be shared by a lineage of self-renewing cell types expressing a range of markers of forebrain lineage.

KW - CELLCYCLE

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UR - http://www.scopus.com/inward/citedby.url?scp=77950502115&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2009.12.049

DO - 10.1016/j.ccr.2009.12.049

M3 - Article

C2 - 20385361

AN - SCOPUS:77950502115

SN - 1535-6108

VL - 17

SP - 362

EP - 375

JO - Cancer cell

JF - Cancer cell

IS - 4

ER -

A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma

Abstract

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Keywords

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