Indian Hedgehog通路在软骨肿瘤发病机制中的研究进展  

Progress of Indian Hedgehog signaling pathway in the pathogenesis of cartilage neoplasms

作　　者：周文灏[1] 燕太强[1] 郭卫[1] 杨荣利[1] 孙义峰[1] 

机构地区：[1]北京大学人民医院骨与软组织肿瘤诊疗中心暨骨肿瘤科,100044

出　　处：《中国骨与关节杂志》2012年第5期522-526,共5页Chinese Journal of Bone and Joint

基　　金：国家自然科学基金项目(81072189)

摘　　要：近30年来大量的研究发现，Hedgehog信号通路不仅参与体内各种细胞的生存、增殖和分化等过程，在正常胚胎发育和器官形成中具有重要作用，同时，该通路的异常活化与多种肿瘤的形成与演进密切相关。针对Hedgehog信号通路的抗肿瘤研究已经成为一个热门的研究方向，将有可能发展出新的治疗手段。本文就此通路与肿瘤的关系及其在软骨肿瘤中的研究成果进行综述。The Hedgehog （HH） signaling pathway, participating in process of survival, proliferation and differentiation in all kinds of ceils in the body, is not only essential in normal embryonic development and organogenesis, but also closely related to the formation and progression of many sorts of neoplasms when activated aberrantly. This pathway is currently recognized as Hedgehog-Ptch-Smo-Gli in summary. Despite the efforts into lots of basic researches continuously improving its molecular regulation network in the past few years, the downstream transduction of it and the specific mechanism of the target genes at tumor onset are yet still unclear. Studies have shown that Indian Hedgehog （IHH） gene is one of the 3 mammal HH homologous genes. Along with its signaling pathway, IHH protein also interacts with other local factors in the microenvironment of the growth plate, especially the parathyroid hormone-related protein （PTHrP）, constituting a negative feedback loop for the regulation of the proliferation and differentiation of chondrocytes, which plays a crucial role in normal bone growth and development. Deregulation of the feedback loop and continuous aberrant activation of the IHH pathway has been found to be involved in the formation and progression of cartilaginous tumors, ranging from benign lesions, such as enchondromas and osteochondromas, to malignant chondrosarcomas. Some of the benign lesions can be the precursors of malignant chondrosareomas, which are notoriously difficult to treat as neither conventional chemotherapy nor radiotherapy is typically effective. Radical surgery, of which the result is still less than ideal because of the high rate of postoperative recurrence and lung metastasis, yet is the mainstay of treatment. As a result of large number of studies in fields of cytogenetics, molecular biology and transgenic mouse models in the past few years, there is a growing understanding of the role of this pathway in the pathogenesis of both the occurrence of primary chondrosarcoma and the

关 键 词：HEDGEHOG信号通路 软骨肿瘤 发病机制 器官形成 胚胎发育 种细胞 抗肿瘤 

分 类 号：R738.3[医药卫生—肿瘤]