Department of Orthopedic Surgery, National Taiwan University Hospital, NO 1, Jen-Ai Road, Taipei 100, Taiwan.
Department of Orthopedic Surgery, National Taiwan University Hospital, NO 1, Jen-Ai Road, Taipei 100, Taiwan.
Biochem Pharmacol. 2018 Sep;155:71-81. doi: 10.1016/j.bcp.2018.06.015. Epub 2018 Jun 15.
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 αvβ3 integrin inhibited cell migration. Moreover, FAK, PI3K, Akt and NF-κB 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 αvβ3 integrin/FAK/PI3K/Akt/NF-κB signaling pathway, which could represent a promising clinical target to improve patient outcome.
骨肉瘤是青少年中最常见的骨恶性肿瘤。骨肉瘤细胞转移到肺部后，由于早期诊断和有效治疗困难，预后非常差。最近，结缔组织生长因子（CTGF）被报道是骨肉瘤转移的关键因素。然而，与 CTGF 定向迁移相关的详细机制在很大程度上仍不清楚。通过对骨肉瘤细胞的体内和体外研究，本研究表明 VCAM-1 的上调和骨肉瘤细胞迁移的增加参与了这一过程。拮抗 αvβ3 整合素抑制细胞迁移。此外，还表明 FAK、PI3K、Akt 和 NF-κB 的激活也参与了 CTGF 介导的骨肉瘤转移。总之，CTGF 通过 αvβ3 整合素/FAK/PI3K/Akt/NF-κB 信号通路促进 VCAM-1 的产生，并进一步诱导骨肉瘤转移，这可能成为改善患者预后的有前途的临床靶点。
