Involvement of matrix metalloproteinase-3 in CCL5/CCR5 pathway of chondrosarcomas metastasis.
CCL5 (previously called RANTES) was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells. It has been reported that the effect of CCL5 is mediated via CCR receptors. We found that human chondrosarcoma tissues had significant expression of the CCL5 and CCR5, which was higher than that in normal cartilage. We also found CCL5 increased the migration and matrix metalloproteinases-3 (MMP)-3 expression in human chondrosarcoma cells (JJ012 cells). In addition, MMP-3 small interfering RNA and inhibitor inhibited the CCL5-induced cell migration. Activations of phosphatidylinositol 3-kinase (PI3K), Akt and NF-kappaB pathways after CCL5 treatment was demonstrated, and CCL5-induced expression of MMP-3 and migration activity was inhibited by the specific inhibitor of PI3K, Akt and NF-kappaB cascades. Taken together, these results indicate that CCL5 and CCR5 interaction enhanced migration of chondrosarcoma cells through the increase of MMP-3 production.
Tang
Chih-Hsin
CH
Department of Pharmacology, China Medical University, Taichung, Taiwan. chtang@mail.cmu.edu.tw
Yamamoto
Ayaho
A
Lin
Yuh-Tzy
YT
Fong
Yi-Chin
YC
Tan
Tzu-Wei
TW
D015153:Blotting, Western; D045744:Cell Line, Tumor; D018946:Chemokine CCL5 / Q000502:physiology*; D002813:Chondrosarcoma / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering
C483024:CCL5 protein, human; D018946:Chemokine CCL5; D034741:RNA, Small Interfering; D019278:Matrix Metalloproteinase 3