Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma.
Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma.
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DOI：
10.1038/s41467-021-21117-3
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发表时间：
2021-02-12
影响因子：
16.6
通讯作者：
Winkler F
中科院分区：
文献类型：
--
作者：
Jung E;Osswald M;Ratliff M;Dogan H;Xie R;Weil S;Hoffmann DC;Kurz FT;Kessler T;Heiland S;von Deimling A;Sahm F;Wick W;Winkler F
血管周围生态位（PVN）和肿瘤微管（TMs）融入多细胞网络与胶质母细胞瘤的进展和治疗耐药性有关，但它们的具体作用尚不清楚。通过对活体小鼠大脑中肿瘤细胞命运和动态的长期跟踪，确定了两种利基的不同治疗反应。PVN（长期静止胶质瘤细胞的优先位置）和网络整合都有助于抵抗放疗和化疗的细胞毒性作用，它们彼此独立，但具有叠加效应。血管周围胶质母细胞瘤细胞特别能够主动修复肿瘤区域的损伤。PVN的数量及其耐药性取决于NOTCH1的熟练表达。反过来，NOTCH1下调通过TM扩展诱导抗性多细胞网络。我们的研究结果确定NOTCH1是胶质瘤中PVN和网络小基之间的中心开关，并且当只有一个小基被靶向时，证明了强大的交叉补偿。血管周围生态位（PVN）和肿瘤微管（TMs）整合到多细胞网络中是否在胶质母细胞瘤的进展和治疗耐药中起不同的作用目前尚不清楚。在这里，作者通过对单个胶质瘤的长期跟踪，证明这两个小生境可以部分地相互补偿，并且两个小生境中的胶质瘤细胞对放疗和化疗具有抗性。
Both the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have been associated with progression and resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of tumor cell fate and dynamics in the live mouse brain, differential therapeutic responses in both niches are determined. Both the PVN, a preferential location of long-term quiescent glioma cells, and network integration facilitate resistance against cytotoxic effects of radiotherapy and chemotherapy—independently of each other, but with additive effects. Perivascular glioblastoma cells are particularly able to actively repair damage to tumor regions. Population of the PVN and resistance in it depend on proficient NOTCH1 expression. In turn, NOTCH1 downregulation induces resistant multicellular networks by TM extension. Our findings identify NOTCH1 as a central switch between the PVN and network niche in glioma, and demonstrate robust cross-compensation when only one niche is targeted. Whether the perivascular niche (PVN) and the integration into multicellular networks by tumor microtubes (TMs) have a different role in glioblastoma progression and resistance to therapies is currently unclear. Here, the authors, by long-term tracking of individual glioma, demonstrate that both niches can partially compensate for each other and that glioma cells localized in both niches are resistant to radio- and chemotherapy.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
64.8
作者：
Capper D;Jones DTW;Sill M;Hovestadt V;Schrimpf D;Sturm D;Koelsche C;Sahm F;Chavez L;Reuss DE;Kratz A;Wefers AK;Huang K;Pajtler KW;Schweizer L;Stichel D;Olar A;Engel NW;Lindenberg K;Harter PN;Braczynski AK;Plate KH;Dohmen H;Garvalov BK;Coras R;Hölsken A;Hewer E;Bewerunge-Hudler M;Schick M;Fischer R;Beschorner R;Schittenhelm J;Staszewski O;Wani K;Varlet P;Pages M;Temming P;Lohmann D;Selt F;Witt H;Milde T;Witt O;Aronica E;Giangaspero F;Rushing E;Scheurlen W;Geisenberger C;Rodriguez FJ;Becker A;Preusser M;Haberler C;Bjerkvig R;Cryan J;Farrell M;Deckert M;Hench J;Frank S;Serrano J;Kannan K;Tsirigos A;Brück W;Hofer S;Brehmer S;Seiz-Rosenhagen M;Hänggi D;Hans V;Rozsnoki S;Hansford JR;Kohlhof P;Kristensen BW;Lechner M;Lopes B;Mawrin C;Ketter R;Kulozik A;Khatib Z;Heppner F;Koch A;Jouvet A;Keohane C;Mühleisen H;Mueller W;Pohl U;Prinz M;Benner A;Zapatka M;Gottardo NG;Driever PH;Kramm CM;Müller HL;Rutkowski S;von Hoff K;Frühwald MC;Gnekow A;Fleischhack G;Tippelt S;Calaminus G;Monoranu CM;Perry A;Jones C;Jacques TS;Radlwimmer B;Gessi M;Pietsch T;Schramm J;Schackert G;Westphal M;Reifenberger G;Wesseling P;Weller M;Collins VP;Blümcke I;Bendszus M;Debus J;Huang A;Jabado N;Northcott PA;Paulus W;Gajjar A;Robinson GW;Taylor MD;Jaunmuktane Z;Ryzhova M;Platten M;Unterberg A;Wick W;Karajannis MA;Mittelbronn M;Acker T;Hartmann C;Aldape K;Schüller U;Buslei R;Lichter P;Kool M;Herold-Mende C;Ellison DW;Hasselblatt M;Snuderl M;Brandner S;Korshunov A;von Deimling A;Pfister SM
通讯作者：
Pfister SM
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
--
作者：
Bayin NS;Frenster JD;Sen R;Si S;Modrek AS;Galifianakis N;Dolgalev I;Ortenzi V;Illa-Bochaca I;Khahera A;Serrano J;Chiriboga L;Zagzag D;Golfinos JG;Doyle W;Tsirigos A;Heguy A;Chesler M;Barcellos-Hoff MH;Snuderl M;Placantonakis DG
通讯作者：
Placantonakis DG
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A