Hedgehog pathway inhibitor-4 suppresses malignant properties of chondrosarcoma cells by disturbing tumor ciliogenesis
Hedgehog pathway inhibitor-4 suppresses malignant properties of chondrosarcoma cells by disturbing tumor ciliogenesis
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Hedgehog 通路抑制剂-4 通过干扰肿瘤纤毛生成来抑制软骨肉瘤细胞的恶性特性
DOI：
10.3892/or.2014.3372
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发表时间：
2014-10-01
期刊：
影响因子：
4.2
通讯作者：
Xu, Kai
中科院分区：
文献类型：
--
作者：
Xiang, Wei;Jiang, Ting;Xu, Kai
软骨肉瘤是一种分泌软骨样基质的恶性骨肿瘤。在临床治疗中，除了手术切除外，没有常用的药物治疗选择。Hedgehog（HH）信号通路是调节正常软骨细胞发育的经典信号通路。为了检测HH通路在软骨肉瘤中的作用，我们使用免疫组织化学方法发现该肿瘤明确表达HH通路相关蛋白。HH通路抑制剂4（HPI-4）能显著抑制软骨肉瘤细胞的增殖、侵袭和迁移能力。此外，HPI-4可明显干扰HH通路介导的纤毛发生，并抑制初级纤毛相关蛋白鞭毛内转运蛋白IFT 88的表达。HH下游效应分子GLI 2被抑制以阻断甲状旁腺相关蛋白并影响MAPK/ERK调节的基质金属蛋白酶（MMP 2和MMP 9）。提示软骨肉瘤中存在激活的HH通路。HPI-4可能是一种新的治疗选择，特异性表达HH途径水平升高的软骨肉瘤。
Chondrosarcoma is a type of malignant bone tumor secreting cartilage-like matrix. In clinical treatment, there is no frequently used drug treatment option except for surgical resection. Hedgehog (HH) pathway is a classical signaling pathway that regulates normal cartilage cell development. In order to detect the role that HH pathway plays in chondrosarcoma, we used immunohistochemistry and found this tumor clearly expressed HH pathway-related proteins. Treatment with HH pathway inhibitor-4 (HPI-4) could significantly decrease human chondrosarcoma cell proliferation, invasion and migration ability. Furthermore, HPI-4 could distinctly disturb HH pathway-mediated ciliogenesis and suppress primary cilia-related protein intraflagellar transport protein IFT88 expression. HH downstream effect molecular GLI2 was restrained to block parathyroid hormone-related protein and affect MAPK/ERK-regulated matrix metalloproteinases (MMP2 and MMP9). These results indicated that activated HH pathway existed in chondrosarcoma. and HPI-4 could be a new therapeutic option specific to chondrosarcoma expressing elevated levels of HH pathway.