Glioblastoma Proximity to the Lateral Ventricle Alters Neurogenic Cell Populations of the Subventricular Zone.
Glioblastoma Proximity to the Lateral Ventricle Alters Neurogenic Cell Populations of the Subventricular Zone.
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DOI：
10.3389/fonc.2021.650316
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发表时间：
2021
影响因子：
4.7
通讯作者：
Guerrero-Cázares H
中科院分区：
文献类型：
--
作者：
Ripari LB;Norton ES;Bodoque-Villar R;Jeanneret S;Lara-Velazquez M;Carrano A;Zarco N;Vazquez-Ramos CA;Quiñones-Hinojosa A;de la Rosa-Prieto C;Guerrero-Cázares H
尽管目前的策略结合了手术、放疗和化疗，但胶质母细胞瘤（GBM）是成人中最常见且侵袭性最强的恶性原发性脑肿瘤。肿瘤位置在患者的预后中起着关键作用，GBM肿瘤位于侧脑室（LV）附近，导致生存预期较差和远端复发率较高。虽然这些患者预后较差的原因尚不清楚，但可能是由于靠近LV侧壁内的脑室下区（SVZ）神经源性龛。我们提出了一种新的啮齿动物模型来分析GBM肿瘤和SVZ内细胞之间的双向信号传导。将表达GFP和荧光素酶的患者来源的GBM细胞移植到免疫抑制小鼠中LV近端、中间和远端的位置。4周后处死小鼠用于肿瘤和SVZ的免疫组织化学分析或维持用于存活分析。GFP+肿瘤块的分析显示，与LV远端对应物相比，LV近端的GBM肿瘤显示出增加的增殖和肿瘤生长水平，并且伴随着中位生存期降低。相反，SVZ内所含的先天性增殖细胞、神经干细胞（NSC）、迁移细胞和祖细胞的数量由于GBM接近LV而减少。这些结果表明，我们的啮齿动物模型能够准确地概括LV相关GBM的几个临床方面，包括肿瘤生长增加和中位生存期降低。此外，我们发现这些成年小鼠中SVZ的神经发生和细胞分裂过程根据肿瘤块的存在和接近而受到负面影响。该模型对于进一步研究GBM和SVZ神经源性细胞群之间的双向信号传导具有重要意义。
Despite current strategies combining surgery, radiation, and chemotherapy, glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Tumor location plays a key role in the prognosis of patients, with GBM tumors located in close proximity to the lateral ventricles (LVs) resulting in worse survival expectancy and higher incidence of distal recurrence. Though the reason for worse prognosis in these patients remains unknown, it may be due to proximity to the subventricular zone (SVZ) neurogenic niche contained within the lateral wall of the LVs. We present a novel rodent model to analyze the bidirectional signaling between GBM tumors and cells contained within the SVZ. Patient-derived GBM cells expressing GFP and luciferase were engrafted at locations proximal, intermediate, and distal to the LVs in immunosuppressed mice. Mice were either sacrificed after 4 weeks for immunohistochemical analysis of the tumor and SVZ or maintained for survival analysis. Analysis of the GFP+ tumor bulk revealed that GBM tumors proximal to the LV show increased levels of proliferation and tumor growth than LV-distal counterparts and is accompanied by decreased median survival. Conversely, numbers of innate proliferative cells, neural stem cells (NSCs), migratory cells and progenitors contained within the SVZ are decreased as a result of GBM proximity to the LV. These results indicate that our rodent model is able to accurately recapitulate several of the clinical aspects of LV-associated GBM, including increased tumor growth and decreased median survival. Additionally, we have found the neurogenic and cell division process of the SVZ in these adult mice is negatively influenced according to the presence and proximity of the tumor mass. This model will be invaluable for further investigation into the bidirectional signaling between GBM and the neurogenic cell populations of the SVZ.
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DOI：
10.1158/1541-7786.mcr-14-0106-t
发表时间：
2014-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Abbadi S;Rodarte JJ;Abutaleb A;Lavell E;Smith CL;Ruff W;Schiller J;Olivi A;Levchenko A;Guerrero-Cazares H;Quinones-Hinojosa A
通讯作者：
Quinones-Hinojosa A
影响因子：
17.1
作者：
Guerrero-Cazares, Hugo;Tzeng, Stephany Y.;Young, Noah P.;Abutaleb, Ameer O.;Quinones-Hinojosa, Alfredo;Green, Jordan J.
通讯作者：
Green, Jordan J.
影响因子：
3
作者：
Chaichana KL;Guerrero-Cazares H;Capilla-Gonzalez V;Zamora-Berridi G;Achanta P;Gonzalez-Perez O;Jallo GI;Garcia-Verdugo JM;Quiñones-Hinojosa A
通讯作者：
Quiñones-Hinojosa A
影响因子：
4.6
作者：
Cantanhede IG;de Oliveira JRM
通讯作者：
de Oliveira JRM
DOI：
10.1016/j.radonc.2015.07.032
发表时间：
2015-08
期刊：
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
影响因子：
--
作者：
Chen L;Chaichana KL;Kleinberg L;Ye X;Quinones-Hinojosa A;Redmond K
通讯作者：
Redmond K