Quiescent Sox2+ Cells Drive Hierarchical Growth and Relapse in Sonic Hedgehog Subgroup Medulloblastoma

被引：217

作者：

Vanner, Robert J. ^{[1
,2
,3
,4
]}

Remke, Marc ^{[1
,2
,3
,5
]}

Gallo, Marco ^{[1
,2
,3
]}

Selvadurai, Hayden J. ^{[1
,2
,3
]}

Coutinho, Fiona ^{[1
,2
,3
,4
]}

Lee, Lilian ^{[1
,2
,3
]}

Kushida, Michelle ^{[1
,2
,3
]}

Head, Renee ^{[1
,2
,3
]}

Morrissy, Sorana ^{[1
,2
,3
]}

Zhu, Xueming ^{[1
,2
,3
]}

Aviv, Tzvi ^{[1
,2
,3
]}

Voisin, Veronique ^{[6
]}

Clarke, Ian D. ^{[1
,2
,3
,7
]}

Li, Yisu ^{[8
]}

Mungall, Andrew J. ^{[8
]}

Moore, Richard A. ^{[8
]}

Ma, Yussanne ^{[8
]}

Jones, Steven J. M. ^{[8
]}

Marra, Marco A. ^{[8
]}

Malkin, David ^{[9
]}

Northcott, Paul A. ^{[10
]}

Kool, Marcel ^{[10
]}

Pfister, Stefan M. ^{[10
,11
]}

Bader, Gary ^{[6
]}

Hochedlinger, Konrad ^{[12
,13
,14
]}

Korshunov, Andrey ^{[15
,16
]}

Taylor, Michael D. ^{[1
,2
,3
,5
]}

Dirks, Peter B. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1L7, Canada

[2] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1L7, Canada

[3] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada

[4] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

[5] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada

[6] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 1A8, Canada

[7] OCAD Univ, Toronto, ON M5T1W1, Canada

[8] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC VSZ 4S6, Canada

[9] Univ Toronto, Div Hematol Oncol, Dept Pediat, HSC, Toronto, ON M6S 1A8, Canada

[10] German Canc Res Ctr DKFZ Heidelberg, Div Pediat Neurooncol, D-69120 Heidelberg, Germany

[11] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany

[12] Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA

[13] Ctr Regenerat Med, Boston, MA 02114 USA

[14] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[15] Heidelberg Univ, Dept Neuropathol, D-69120 Heidelberg, Germany

[16] DKFZ, German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-69120 Heidelberg, Germany

来源：

CANCER CELL | 2014年 / 26卷 / 01期

基金：

加拿大健康研究院;

关键词：

CANCER STEM-CELLS; PATHWAY INHIBITOR; INITIATING CELLS; PROGENITOR CELLS; MELANOMA-CELLS; MOUSE MODEL; ADULT STEM; TUMOR; MARKER; IDENTIFICATION;

D O I：

10.1016/j.ccr.2014.05.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Functional heterogeneity within tumors presents a significant therapeutic challenge. Here we show that quiescent, therapy-resistant Sox(2+) cells propagate sonic hedgehog subgroup nnedulloblastoma by a mechanism that mirrors a neurogenic program. Rare Sox(2+) cells produce rapidly cycling doublecortin(+) progenitors that, together with their postmitotic progeny expressing NeuN, comprise tumor bulk. Sox(2+) cells are enriched following anti-mitotic chemotherapy and Smoothened inhibition, creating a reservoir for tumor regrowth. Lineage traces from Sox(2+) cells increase following treatment, suggesting that this population is responsible for relapse. Targeting Sox(2+) cells with the antineoplastic mithramycin abrogated tumor growth. Addressing functional heterogeneity and eliminating Sox(2+) cells presents a promising therapeutic paradigm for treatment of sonic hedgehog subgroup medulloblastoma.

引用

页码：33 / 47

页数：15

共 22 条

[1] QUIESCENT SOX2+ CELLS UNDERLIE SHH MEDULLOBLASTOMA GROWTH AND RELAPSE
不详
[J]. CANCER DISCOVERY, 2014, 4 (08) : 868 - 868
[2] SOX2+ CELLS: THE PERPETRATORS OF MEDULLOBLASTOMA RELAPSE
Swiderska-Syn, Marzena
Mir-Pedrol, Julia
Rodriguez-Blanco, Jezabel
[J]. NEURO-ONCOLOGY, 2022, 24 : 109 - 109
[3] Noncanonical activation of GLI signaling in SOX2+ cells drives medulloblastoma relapse
Swiderska-Syn, Marzena
Mir-Pedrol, Julia
Oles, Alexander
Schleuger, Olga
Salvador, April D.
Greiner, Sean M.
Seward, Cara
Yang, Fan
Babcock, Benjamin R.
Shen, Chen
Wynn, Daniel T.
Sanchez-Mejias, Avencia
Gershon, Timothy R.
Martin, Vanesa
McCrea, Heather J.
Lindsey, Kathryn G.
Krieg, Carsten
Rodriguez-Blanco, Jezabel
[J]. SCIENCE ADVANCES, 2022, 8 (29)
[4] Sox2+ cells in Sonic Hedgehog-subtype medulloblastoma resist p53-mediated cell-cycle arrest response and drive therapy-induced recurrence
Treisman, Daniel M.
Li, Yinghua
Pierce, Brianna R.
Li, Chaoyang
Chervenak, Andrew P.
Tomasek, Gerald J.
Lozano, Guillermina
Zheng, Xiaoyan
Kool, Marcel
Zhu, Yuan
[J]. NEURO-ONCOLOGY ADVANCES, 2019, 1 (01)
[5] Sox2 Requirement in Sonic Hedgehog-Associated Medulloblastoma
Ahlfeld, Julia
Favaro, Rebecca
Pagella, Pierfrancesco
Kretzschmar, Hans A.
Nicolis, Silvia
Schueller, Ulrich
[J]. CANCER RESEARCH, 2013, 73 (12) : 3796 - 3807
[6] ASTROCYTIC SOX2+ CELLS RELAY IN NON-CANONICAL GLI SIGNALING TO FACILITATE MEDULLOBLASTOMA RELAPSE.
Swiderska-Syn, Marzena
Mir-Pedrol, Julia
Oles, Alexander
Babcock, Benjamin
Martin, Vanesa
Krieg, Carsten
Gershon, Timothy
McCrea, Heather
Rodriguez-Blanco, Jezabel
[J]. NEURO-ONCOLOGY, 2022, 24 : 36 - 37
[7] MYC Drives Group 3 Medulloblastoma through Transformation of Sox2+ Astrocyte Progenitor Cells
Tao, Ran
Murad, Najiba
Xu, Zhenhua
Zhang, Peng
Okonechnikov, Konstantin
Kool, Marcel
Rivero-Hinojosa, Samuel
Lazarski, Christopher
Zheng, Pan
Liu, Yang
Eberhart, Charles G.
Rood, Brian R.
Packer, Roger
Pei, Yanxin
[J]. CANCER RESEARCH, 2019, 79 (08) : 1967 - 1980
[8] Sox2, a marker for stem-like tumor cells in skin squamous cell carcinoma and hedgehog subgroup medulloblastoma
Becher, Oren J.
Holland, Eric C.
[J]. EMBO JOURNAL, 2014, 33 (18): : 1984 - 1986
[9] Suppressing recurrence in Sonic Hedgehog subgroup medulloblastoma using the OLIG2 inhibitor CT-179
Yuchen Li
Chaemin Lim
Taylor Dismuke
Daniel S. Malawsky
Sho Oasa
Zara C. Bruce
Carolin Offenhäuser
Ulrich Baumgartner
Rochelle C. J. D’Souza
Stacey L. Edwards
Juliet D. French
Lucy S. H. Ock
Sneha Nair
Haran Sivakumaran
Lachlan Harris
Andrey P. Tikunov
Duhyeong Hwang
Coral Del Mar Alicea Pauneto
Mellissa Maybury
Timothy Hassall
Brandon Wainwright
Santosh Kesari
Gregory Stein
Michael Piper
Terrance G. Johns
Marina Sokolsky-Papkov
Lars Terenius
Vladana Vukojević
Leon F. McSwain
Timothy R. Gershon
Bryan W. Day
[J]. Nature Communications, 16 (1)
[10] Hepatocyte growth factor and Sonic Hedgehog expression in cerebellar neural progenitor cells costimulate medulloblastoma initiation and growth
Binning, Mandy J.
Niazi, Toba
Pedone, Carolyn A.
Lal, Bachchu
Eberhart, Charles G.
Kim, K. Jin
Laterra, John
Fults, Daniel W.
[J]. CANCER RESEARCH, 2008, 68 (19) : 7838 - 7845

← 1 2 3 →