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 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 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。

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.