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Role of SerpinA3 in the response of glioblastoma to cerebrospinal fluid

SerpinA3在胶质母细胞瘤对脑脊液反应中的作用

基本信息

批准号：
9925463
负责人：
Hugo Guerrero-Cazares
金额：
$ 1.24万
依托单位：
MAYO CLINIC JACKSONVILLE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9925463
关键词：
Adult Affect Amino Acids Animal Model Binding Biocompatible Materials Brain Glioblastoma Brain Neoplasms Cell Proliferation Cell Survival Cells Cellular Structures Cerebrospinal Fluid ChIP-seq DNA DNA Binding DNA Sequence Diagnosis Distal Distant Excision Expectancy Exposure to Extracellular Protein Foundations Gene Chips Gene Expression Genes Genomic Segment Glioblastoma Hippocampus (Brain)Human Hydrogels Implant In Vitro Investigation Laboratories Lead Location Malignant - descriptor Malignant Neoplasms Malignant neoplasm of brain Malignant neoplasm of liver Malignant neoplasm of pancreas Mass Spectrum Analysis Modeling Mus Nuclear Pore Complex Operative Surgical Procedures Outcome Patients Phenotype Primary Brain Neoplasms Proliferating Proteins Radiation Radio Recurrence Reporting Role Serine Protease Serine Proteinase Inhibitors Survival Rate Testing Therapeutic Therapeutic Intervention Tumor Initiators Undifferentiated alpha 1-Antichymotrypsin base brain tissue cell motility chemotherapy combinatorial experimental study fetal immunosuppressed in vivo lateral ventricle loss of function lymphatic cancer malignant breast neoplasm malignant phenotype migration negative affect nerve stem cell neural implant outcome forecast overexpression response self-renewal standard of care subventricular zone targeted treatment tissue culture tumor virtual whole genome

项目摘要

ROLE OF SERPINA3 IN THE RESPONSE OF GLIOBLASTOMA TO CEREBROSPINAL FLUID Project Summary Glioblastoma (GBM) is the most common, aggressive and proliferative primary brain tumor in adults despite current therapeutic strategies that combine surgery, radio, and chemotherapy. The high invasive capacity of GBM makes total surgical resection virtually impossible, resulting in an extremely high recurrence rate. The ability to form a new tumor resides in a subpopulation of cells within the GBM called brain tumor initiating cells (BTICs). BTICs are undifferentiated cells with self-renewing and pluripotential capacity, similar to neural stem cells (NSCs), but with the added ability of forming tumors in vivo. Our group and others have reported that among primary GBMs, those that are located in close proximity to the lateral ventricles (LV) present multiple factors, including increased recurrence at distant locations, that negatively affect patients' survival. The cause for a worse outcome in patients suffering LV-proximal GBMs is not known. Possible explanations may involve the proximity of these tumors to the cerebrospinal fluid (CSF) and neurogenic niche in the sub-ventricular zone (SVZ). In preliminary studies we have demonstrated that CSF stimulation increases the invasive capacity of GBM cells. Furthermore CSF stimulation induces the overexpression of the serine protease inhibitor SerpinA3. Here we propose to study the role of SerpinA3 in the response of GBM cells to CSF. Upon completion of this study we will have gained a better understanding of the effects of CSF on GBM cells through SerpinA3. Ultimately, we hope to reveal specific targets for therapeutic intervention to lead to increased survival in patients with GBM.

Serpina3在胶质母细胞瘤对脑脊液反应中的作用项目摘要胶质母细胞瘤（GBM）是成人中最常见、最具侵袭性和增殖性的原发性脑肿瘤尽管目前的治疗策略结合了联合收割机手术、放疗和化疗。高侵袭 GBM的容量使得完全手术切除几乎是不可能的，导致极高的复发率形成新肿瘤的能力存在于GBM内的细胞亚群中，称为GBM。脑肿瘤起始细胞（BTIC）。BTIC是具有自我更新和多潜能的未分化细胞，干细胞是神经干细胞的一种，它具有类似于神经干细胞（NSC）的能力，但具有在体内形成肿瘤的能力。我们小组和其他人报告说，在主要的GBM中，那些位于靠近侧脑室（LV）存在多种因素，包括远处复发增加，对患者的生存有负面影响。左室近端病变患者结局更差的原因 GBM是未知的。可能的解释可能涉及这些肿瘤的接近，脑脊液（CSF）和脑室下区（SVZ）的神经源性龛。在初步研究中我们已经证明CSF刺激增加GBM细胞的侵袭能力。此外 CSF刺激诱导丝氨酸蛋白酶抑制剂SerpinA3的过表达。在这里我们建议研究SerpinA3在GBM细胞对CSF应答中的作用。完成这项研究后，我们将已经通过SerpinA3更好地了解CSF对GBM细胞的影响。最终我们希望揭示治疗干预的特定靶点，以增加患有 GBM。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sex-Specific Differences in Glioblastoma.

DOI：
10.3390/cells10071783
发表时间：
2021-07-14
期刊：
Cells
影响因子：
6
作者：
Carrano A;Juarez JJ;Incontri D;Ibarra A;Guerrero Cazares H
通讯作者：
Guerrero Cazares H

Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy.

DOI：
10.3389/fonc.2021.624145
发表时间：
2021
期刊：
Frontiers in oncology
影响因子：
4.7
作者：
Carrano A;Zarco N;Phillipps J;Lara-Velazquez M;Suarez-Meade P;Norton ES;Chaichana KL;Quiñones-Hinojosa A;Asmann YW;Guerrero-Cázares H
通讯作者：
Guerrero-Cázares H