Loading…

CCN6-mediated MMP-9 activation enhances metastatic potential of human chondrosarcoma

Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. WNT1-inducible signaling pathway protein-3 (WISP-3, also termed CCN6) belongs to the CCN family of proteins and is implicated in the regulation of various cellular functions, such as cell proliferation, differentiation, an...

Full description

Saved in:
Bibliographic Details
Published in:Cell death & disease 2018-09, Vol.9 (10), p.955-13, Article 955
Main Authors: Tzeng, Huey-En, Tang, Chih-Hsin, Wu, Sz-Hua, Chen, Hsien-Te, Fong, Yi-Chin, Lu, Yung-Chang, Chen, Wei-Cheng, Huang, Hsien-Da, Lin, Chih-Yang, Wang, Shih-Wei
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. WNT1-inducible signaling pathway protein-3 (WISP-3, also termed CCN6) belongs to the CCN family of proteins and is implicated in the regulation of various cellular functions, such as cell proliferation, differentiation, and migration. It is unknown as to whether CCN6 affects human chondrosarcoma metastasis. We show how CCN6 promotes chondrosarcoma cell migration and invasion via matrix metallopeptidase-9 (MMP)-9 expression. These effects were abolished by pretreatment of chondrosarcoma cells with PI3K, Akt, mTOR, and NF-κB inhibitors or short interfering (si)RNAs. Our investigations indicate that CCN6 facilitates metastasis through the PI3K/Akt/mTOR/NF-κB signaling pathway. CCN6 and MMP-9 expression was markedly increased in the highly migratory JJ012(S10) cell line compared with the primordial cell line (JJ012) in both in vitro and in vivo experiments. CCN6 knockdown suppressed MMP-9 production in JJ012(S10) cells and attenuated cell migration and invasion ability. Importantly, CCN6 knockdown profoundly inhibited chondrosarcoma cell metastasis to lung. Our findings reveal an important mechanism underlying CCN6-induced metastasis and they highlight the clinical significance between CCN6 and MMP-9 in regard to human chondrosarcoma. CCN6 appears to be a promising therapeutic target in chondrosarcoma metastasis.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-018-1008-9