Role of Human Cerebrospinal Fluid Chemokines in the Invasiveness of Human Glioblastoma

人脑脊液趋化因子在人胶质母细胞瘤侵袭性中的作用

• 批准号: 9544413
• 负责人: Hugo Guerrero-Cazares
• 金额: $ 0.34万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9544413
• 关键词: Adult; Affect; Aggressive behavior; Behavior; Brain Neoplasms; Cell Culture Techniques; Cells; Cerebrospinal Fluid; Choroid; Data; Distant; Drosophila sli protein; Excision; Foundations; Fractionation; Glioblastoma; Glioma; Goals; Human; In Vitro; Intrathecal Injections; Ipsilateral; Lead; Ligands; Location; Malignant - descriptor; Malignant Neoplasms; Modeling; Mus; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Pilot Projects; Play; Population; Primary Brain Neoplasms; Radiation; Radiation therapy; Radio; Recurrence; Reporting; Research; Rodent; Role; Sampling; Scheme; Signal Transduction; Speed; Survival Rate; Testing; Therapeutic; Therapeutic Intervention; Tissues; Tumor Cell Invasion; Tumor Initiators; Undifferentiated; Ventricular; cancer cell; cell motility; cerebrospinal fluid flow; chemokine; chemotherapy; human migration; human tissue; improved; in vivo; innovation; interest; knock-down; lateral ventricle; migration; negative affect; nerve stem cell; outcome forecast; programs; receptor; response; self-renewal; subventricular zone; targeted treatment; therapeutic target; tumor; tumor growth; tumor progression; virtual

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, with the added ability of forming tumors in vivo. Our group and others have reported that among primary GBMs, those located in close proximity to the lateral ventricles (LV) present multiple distinct features, including increased recurrence at distant locations, which negatively affect patients' survival. The cause for worse outcomes 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 a pilot study, we have determined that human non-cancer CSF repels BTICs migration in vitro. The molecules in the CSF responsible for this effect are not known. Here we propose to study the interactions between BTICs and different fractions of CSF. We hypothesize that CSF can induce a more aggressive behavior of GBM cells. We will perform this research using intraoperative human tissue. Upon completion of this study we will have gained a better understanding of the effects of CSF on GBM cells and will have discovered possible factors within CSF which influence BTICs and cancer progression. Ultimately, we hope to reveal specific targets for therapeutic intervention leading to increased survival in patients with GBM.

项目概要 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 结合手术、放射和化疗的治疗策略。 GBM 的高侵袭能力使得总 手术切除几乎不可能，导致复发率极高。形成新肿瘤的能力 存在于 GBM 内称为脑肿瘤起始细胞 (BTIC) 的细胞亚群中。 BTIC 未分化 具有自我更新和多能能力的细胞，还具有在体内形成肿瘤的能力。我们组和 其他人报告说，在原发性 GBM 中，那些靠近侧脑室 (LV) 的 GBM 存在 多种不同的特征，包括远处复发率增加，这对患者的生存产生负面影响。 左心室近端 GBM 患者预后较差的原因尚不清楚。可能的解释可能是 涉及这些肿瘤靠近脑脊液 (CSF) 和脑室下区的神经源性生态位 （SVZ）。在一项初步研究中，我们确定人类非癌症脑脊液可排斥 BTIC 体外迁移。分子 脑脊液中造成这种效应的原因尚不清楚。在这里，我们建议研究 BTIC 和 脑脊液的不同部分。我们假设脑脊液可以诱导 GBM 细胞更具攻击性的行为。我们将 使用术中人体组织进行这项研究。完成本次学习后，我们将获得更好的 了解 CSF 对 GBM 细胞的影响，并将发现 CSF 内影响的可能因素 BTIC 和癌症进展。最终，我们希望揭示治疗干预的具体目标，从而导致 GBM 患者的生存率增加。