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

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.

Keywords: CTGF; Cell migration; Osteosarcoma metastasis; VCAM-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / chemically induced
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Connective Tissue Growth Factor / toxicity*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Osteosarcoma / chemically induced
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*
  • Vascular Cell Adhesion Molecule-1 / genetics


  • CCN2 protein, human
  • Vascular Cell Adhesion Molecule-1
  • Connective Tissue Growth Factor