Connective tissue growth factor stimulates osteosarcoma cell migration and induces osteosarcoma metastasis by upregulating VCAM-1 expression

Osteosarcoma is the most common bone malignancy that occurs in the young population. After osteosarcoma cells metastasize to the lung, prognosis is very poor owing to difficulties in early diagnosis and effective treatment. Recently, connective tissue growth factor (CTGF) was reported to be a critical contributor to osteosarcoma metastasis. However, the detailed mechanism associated with CTGF-directed migration in bone neoplasms is still mostly unknown. Through the in vivo and in vitro examination of osteosarcoma cells, this study suggests that VCAM-1 up-regulation and increased osteosarcoma cell migration are involved in this process. Antagonizing alpha v beta 3 integrin inhibited cell migration. Moreover, FAK, PI3K, Akt and NF-kappa B activation were also shown to be involved in CTGF-mediated osteosarcoma metastasis. Taken together, CTGF promotes VCAM-1 production and further induces osteosarcoma metastasis via the alpha v beta 3 integrin/FAK/PI3K/Akt/NF-kappa B signaling pathway, which could represent a promising clinical target to improve patient outcome.