利用骨形成蛋白2抑制骨肉瘤的分化疗法

项目名称： 利用骨形成蛋白2抑制骨肉瘤的分化疗法

项目编号： No.31470045

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 林嘉盈

作者单位： 北京航空航天大学

项目金额： 30万元

中文摘要： 目前临床上禁止将骨形成蛋白2应用于骨肿瘤外科，主要的疑虑是其可能会导致癌症的生长与扩张。近年来的研究表明肿瘤的发生可能是由一小群肿瘤细胞所诱发，它们表现出许多类似干细胞的特性，支持肿瘤的生长、复发甚至阻抗癌症的治疗。申请人的研究团队发表了许多证据，指出将骨形成蛋白应用于由癌干细胞组成的非均质肿瘤，将可诱发这些癌干细胞的成骨分化，进而减缓肿瘤的生长以及增进其对治疗药物的反应。因此，我们希望通过本研究来进一步推动此科研成果到临床医学的转化。本研究拟将犬的骨肉瘤做为临床前先期测试的对象，来评估骨形成蛋白作为分化疗法的可行性，将达成（1）对骨形成蛋白诱发后，受肿瘤侵犯及手术切除骨骼新生组织的组成，及内含细胞的致癌能力的分析；（2）对接受骨形成蛋白进行重建的骨骼力学功能的测试等主要研究目标。

中文关键词： 骨肉瘤；骨形成蛋白2；肿瘤干细胞；分化疗法；

英文摘要： Osteosarcoma can cause severe symptoms associated with impeded bone growth. Invasion of skeleton, such as spine and limbs, is commonly accompanied with complications such as neural deficits and pathological fracture, and thus requires surgical stabilization. Recombinant human bone morphogenetic proteins (BMP) have been recently approved to augment spinal fusion and recalcitrant long-bone non-unions for their equivalent or superior efficacy to autogenous bone graft in enhancing bony fusion. Nonetheless, the use of BMP-2 is contraindicated in surgery for bone tumors due to concerns that this anabolic growth factor may cause tumor proliferation. Recent evidence suggests that there is a small fraction of tumor-initiating cells present in a variety of cancers, including bone tumors. These cells express properties resembling stem cells (so-called cancer stem cells) that might be responsible for tumor growth, recurrence, and resistance to treatment. Our current investigations suggest that exposure of heterogeneous populations of cancer cells containing stem-like cells to BMPs can induce osteogenic differentiation of the stem-like cells and thereby reduce tumor growth and improve responsiveness to treatment. We hypothesize that BMP-2 induction reduces tumorigenic capacity of osteosarcoma while promoting osseous reunion

英文关键词： osteosarcoma；BMP-2；cancer stem cells；differentiation therapy；