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

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

doi:10.3892/or.2014.3372

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

Authors:
- Wei Xiang
- Ting Jiang
- Fengjing Guo
- Chen Gong
- Kaixiang Yang
- Yingxing Wu
- Xin Huang
- Weiting Cheng
- Kai Xu
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Affiliations: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Oncology, Wuhan Integrated Traditional Chinese Medicine and Western Medicine Hospital, Wuhan No. 1 Hospital, Wuhan, Hubei 430030, P.R. China
Published online on: July 31, 2014 https://doi.org/10.3892/or.2014.3372
Pages: 1622-1630

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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.

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