Oncology Reports 2014-10-01

Hedgehog pathway inhibitor-4 suppresses malignant properties of chondrosarcoma cells by disturbing tumor ciliogenesis.

Wei Xiang, Ting Jiang, Fengjing Guo, Chen Gong, Kaixiang Yang, Yingxing Wu, Xin Huang, Weiting Cheng, Kai Xu

Index: Oncol. Rep. 32(4) , 1622-30, (2014)

Full Text: HTML

Abstract

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.