Therapeutic modulation with thrombospondin-1

性状（由申请方提供）：血栓反应蛋白-1（TSP-1）是一种内源性血管生成抑制剂，通常由多种细胞类型分泌。已经发现各种来源的肿瘤，包括胶质母细胞瘤，下调血小板反应蛋白-1（TSP-1）的表达。我们以前已经表明，TSP-1在人胶质母细胞瘤细胞中的过表达降低了免疫功能低下小鼠的致瘤性，这显然是由于抑制血管生成。我们建议通过确定在预先存在的脑肿瘤中诱导TSP-1表达是否会导致皮下和颅内胶质瘤模型中肿瘤生长的停滞或逆转来扩展我们的致瘤性研究。此外，我们计划研究仅含有1型重复序列的mini-TSP-1蛋白是否具有与全长TSP-1相当的抗血管生成活性。我们最终将使用神经祖细胞作为治疗工具，在颅内胶质瘤模型中递送TSP-1或mini-TSP-1。通过这种方法，在肿瘤部位将理想地实现稳定和有效水平的TSP-1或mini-TSP-1。这种治疗方式的实验成功将很容易适应临床情况，并可能导致胶质母细胞瘤和其他类型癌症的新的和高效的治疗。

DESCRIPTION (provided by applicant): Thrombospondin-1 (TSP-1), an endogenous angiogenisis inhibitor, is normally secreted by many cell types. Tumors of various origins, including glioblastomas, have been found to down-regulate thrombospondin-1 (TSP-1) expression. We have previously shown that overexpression of TSP-1 in human glioblastoma cells reduces their tumorigenicity in immunocompromised mice, apparently due to inhibition of angiogenesis. We propose to extend our tumorigenicity studies by determining whether induced expression of TSP-1 in a pre-existing brain tumor will result in arrest or reversal of tumor growth in subcutaneous and intracranial glioma models. Additionally, we plan to investigate if mini-TSP-1 proteins containing solely type 1 repeats will have anti-angiogenic activities comparable to full length TSP-1. We will ultimately use neural progenitor cells as a therapeutic tool to deliver TSP-1 or mini-TSP-1 in an intracranial glioma model. With this approach steady and efficacious levels of TSP-1 or mini-TSP-1 will be ideally achievable at the tumor sites. Experimental success in this treatment modality will be readily adaptable to a clinical situation, and could lead to new and highly effective treatment for glioblastomas and other types of cancer.