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 项目摘要 摘要胶质母细胞瘤是成人最常见、最具侵袭性和增殖性的原发脑肿瘤。 尽管目前的治疗策略是手术、放射和化疗相结合。高度侵袭性 基底膜的容量使完全手术切除几乎不可能，导致极高的 复发率。形成新肿瘤的能力存在于基底膜内称为 脑肿瘤起始细胞(BTICs)。BTIC是一种具有自我更新和多潜能的未分化细胞 能力，类似于神经干细胞(NSCs)，但增加了在体内形成肿瘤的能力。我们的 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)呈现多种因素，包括远处复发增加， 对患者的生存有负面影响。左心室近端患者预后较差的原因 GBMS未知。可能的解释可能涉及到这些肿瘤靠近 脑脊液(CSF)和脑室下区神经源性窝穴(SVZ)。在初步研究中 我们已经证明了脑脊液刺激增加了基底膜细胞的侵袭能力。更有甚者 脑脊液刺激可诱导丝氨酸蛋白酶抑制因子SerpinA3的过度表达。在这里，我们建议 目的：研究SerpinA3在GBM细胞对脑脊液反应中的作用。在这项研究完成后，我们会 通过SerpinA3更好地了解了脑脊液对GBM细胞的影响。最终，我们 希望揭示治疗干预的特定靶点，以提高患者的存活率 GBM。

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.