Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression.
Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression.
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DOI：
10.1038/s41467-022-31340-1
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发表时间：
2022-06-24
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
Intra-tumoral heterogeneity is a hallmark of glioblastoma that challenges treatment efficacy. However, the mechanisms that set up tumor heterogeneity and tumor cell migration remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a specific, actionable, spatial transcriptomic signature. Oncostreams are dynamic multicellular fascicles of spindle-like and aligned cells with mesenchymal properties, detected using ex vivo explants and in vivo intravital imaging. Their density correlates with tumor aggressiveness in genetically engineered mouse glioma models, and high grade human gliomas. Oncostreams facilitate the intra-tumoral distribution of tumoral and non-tumoral cells, and potentially the collective invasion of the normal brain. These fascicles are defined by a specific molecular signature that regulates their organization and function. Oncostreams structure and function depend on overexpression of COL1A1. Col1a1 is a central gene in the dynamic organization of glioma mesenchymal transformation, and a powerful regulator of glioma malignant behavior. Inhibition of Col1a1 eliminates oncostreams, reprograms the malignant histopathological phenotype, reduces expression of the mesenchymal associated genes, induces changes in the tumor microenvironment and prolongs animal survival. Oncostreams represent a pathological marker of potential value for diagnosis, prognosis, and treatment. It is essential to improve our understanding of the features that influence aggressiveness and invasion in high grade gliomas (HGG). Here, the authors characterize dynamic anatomical structures in HGG called oncostreams, which are associated with tumor growth and are regulated by COL1A1.
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DOI：
10.1002/advs.202002015
发表时间：
2020-11
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Azam Z;To ST;Tannous BA
通讯作者：
Tannous BA
影响因子：
4
作者：
Deisboeck, Thomas S.;Couzin, Iain D.
通讯作者：
Couzin, Iain D.
DOI：
10.1056/nejmoa1402121
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cancer Genome Atlas Research Network;Brat DJ;Verhaak RG;Aldape KD;Yung WK;Salama SR;Cooper LA;Rheinbay E;Miller CR;Vitucci M;Morozova O;Robertson AG;Noushmehr H;Laird PW;Cherniack AD;Akbani R;Huse JT;Ciriello G;Poisson LM;Barnholtz-Sloan JS;Berger MS;Brennan C;Colen RR;Colman H;Flanders AE;Giannini C;Grifford M;Iavarone A;Jain R;Joseph I;Kim J;Kasaian K;Mikkelsen T;Murray BA;O'Neill BP;Pachter L;Parsons DW;Sougnez C;Sulman EP;Vandenberg SR;Van Meir EG;von Deimling A;Zhang H;Crain D;Lau K;Mallery D;Morris S;Paulauskis J;Penny R;Shelton T;Sherman M;Yena P;Black A;Bowen J;Dicostanzo K;Gastier-Foster J;Leraas KM;Lichtenberg TM;Pierson CR;Ramirez NC;Taylor C;Weaver S;Wise L;Zmuda E;Davidsen T;Demchok JA;Eley G;Ferguson ML;Hutter CM;Mills Shaw KR;Ozenberger BA;Sheth M;Sofia HJ;Tarnuzzer R;Wang Z;Yang L;Zenklusen JC;Ayala B;Baboud J;Chudamani S;Jensen MA;Liu J;Pihl T;Raman R;Wan Y;Wu Y;Ally A;Auman JT;Balasundaram M;Balu S;Baylin SB;Beroukhim R;Bootwalla MS;Bowlby R;Bristow CA;Brooks D;Butterfield Y;Carlsen R;Carter S;Chin L;Chu A;Chuah E;Cibulskis K;Clarke A;Coetzee SG;Dhalla N;Fennell T;Fisher S;Gabriel S;Getz G;Gibbs R;Guin R;Hadjipanayis A;Hayes DN;Hinoue T;Hoadley K;Holt RA;Hoyle AP;Jefferys SR;Jones S;Jones CD;Kucherlapati R;Lai PH;Lander E;Lee S;Lichtenstein L;Ma Y;Maglinte DT;Mahadeshwar HS;Marra MA;Mayo M;Meng S;Meyerson ML;Mieczkowski PA;Moore RA;Mose LE;Mungall AJ;Pantazi A;Parfenov M;Park PJ;Parker JS;Perou CM;Protopopov A;Ren X;Roach J;Sabedot TS;Schein J;Schumacher SE;Seidman JG;Seth S;Shen H;Simons JV;Sipahimalani P;Soloway MG;Song X;Sun H;Tabak B;Tam A;Tan D;Tang J;Thiessen N;Triche T Jr;Van Den Berg DJ;Veluvolu U;Waring S;Weisenberger DJ;Wilkerson MD;Wong T;Wu J;Xi L;Xu AW;Yang L;Zack TI;Zhang J;Aksoy BA;Arachchi H;Benz C;Bernard B;Carlin D;Cho J;DiCara D;Frazer S;Fuller GN;Gao J;Gehlenborg N;Haussler D;Heiman DI;Iype L;Jacobsen A;Ju Z;Katzman S;Kim H;Knijnenburg T;Kreisberg RB;Lawrence MS;Lee W;Leinonen K;Lin P;Ling S;Liu W;Liu Y;Liu Y;Lu Y;Mills G;Ng S;Noble MS;Paull E;Rao A;Reynolds S;Saksena G;Sanborn Z;Sander C;Schultz N;Senbabaoglu Y;Shen R;Shmulevich I;Sinha R;Stuart J;Sumer SO;Sun Y;Tasman N;Taylor BS;Voet D;Weinhold N;Weinstein JN;Yang D;Yoshihara K;Zheng S;Zhang W;Zou L;Abel T;Sadeghi S;Cohen ML;Eschbacher J;Hattab EM;Raghunathan A;Schniederjan MJ;Aziz D;Barnett G;Barrett W;Bigner DD;Boice L;Brewer C;Calatozzolo C;Campos B;Carlotti CG Jr;Chan TA;Cuppini L;Curley E;Cuzzubbo S;Devine K;DiMeco F;Duell R;Elder JB;Fehrenbach A;Finocchiaro G;Friedman W;Fulop J;Gardner J;Hermes B;Herold-Mende C;Jungk C;Kendler A;Lehman NL;Lipp E;Liu O;Mandt R;McGraw M;Mclendon R;McPherson C;Neder L;Nguyen P;Noss A;Nunziata R;Ostrom QT;Palmer C;Perin A;Pollo B;Potapov A;Potapova O;Rathmell WK;Rotin D;Scarpace L;Schilero C;Senecal K;Shimmel K;Shurkhay V;Sifri S;Singh R;Sloan AE;Smolenski K;Staugaitis SM;Steele R;Thorne L;Tirapelli DP;Unterberg A;Vallurupalli M;Wang Y;Warnick R;Williams F;Wolinsky Y;Bell S;Rosenberg M;Stewart C;Huang F;Grimsby JL;Radenbaugh AJ;Zhang J
通讯作者：
Zhang J
影响因子：
64.5
作者：
Ceccarelli M;Barthel FP;Malta TM;Sabedot TS;Salama SR;Murray BA;Morozova O;Newton Y;Radenbaugh A;Pagnotta SM;Anjum S;Wang J;Manyam G;Zoppoli P;Ling S;Rao AA;Grifford M;Cherniack AD;Zhang H;Poisson L;Carlotti CG Jr;Tirapelli DP;Rao A;Mikkelsen T;Lau CC;Yung WK;Rabadan R;Huse J;Brat DJ;Lehman NL;Barnholtz-Sloan JS;Zheng S;Hess K;Rao G;Meyerson M;Beroukhim R;Cooper L;Akbani R;Wrensch M;Haussler D;Aldape KD;Laird PW;Gutmann DH;TCGA Research Network;Noushmehr H;Iavarone A;Verhaak RG
通讯作者：
Verhaak RG
影响因子：
64.8
作者：
通讯作者：
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