Tumor Biology

, Volume 36, Issue 3, pp 2185–2191 | Cite as

Vascular endothelial growth factor B coordinates metastasis of non-small cell lung cancer

  • Gang Liu
  • Shengbao Xu
  • Fanglei Jiao
  • Tao Ren
  • Qinchuan Li
Research Article


Neovascularization is critical for the invasion and metastasis of non-small cell lung cancer (NSCLC). However, the molecular mechanism underlying the control of neovascularization of NSCLC is not completely understood. Both vascular endothelial growth factor B (VEGF-B) and matrix metalloproteinases 9 (MMP9) play essential roles in neovascularization of NSCLC. Here, we examined whether VEGF-B and MMP9 may affect each other to coordinate the neovascularization process in NSCLC. We found strong positive correlation of VEGF-B and MMP9 levels in the NSCLC from the patients. Moreover, patients that had NSCLC with metastasis had significantly higher levels of VEGF-B and MMP9 in the primary cancer. Using a human NSCLC line A549, we found that overexpression of VEGF-B increased expression of MMP9, while inhibition of VEGF-B decreased expression of MMP9. On the other hand, overexpression of MMP9 increased expression of VEGF-B, while inhibition of MMP9 decreased expression of VEGF-B. These data suggest that expression of VEGF-B and MMP9 may activate each other to enhance neovascularization. We then analyzed the underlying mechanism. Application of a specific ERK/MAPK inhibitor but not a PI3K/Akt inhibitor to VEGF-B-overexpressing A549 cells substantially abolished the effect of VEGF-B on MMP9 activation, while application of a specific PI3K/Akt inhibitor but not an ERK/MAPK inhibitor to MMP9-overexpressing A549 cells substantially abolished the effect of MMP9 on VEGF-B activation, suggesting that VEGF-B may activate MMP9 via ERK/MAPK signaling pathway, while MMP9 may activate VEGF-B via PI3K/Akt signaling pathway. Thus, our data highlight a coordinating relationship between VEGF-B and MMP9 in the regulation of neovascularization in NSCLC.


Vascular endothelial growth factor B (VEGF-B) Matrix metalloproteinases 9 (MMP9), PI3K ERK/MAPK Non-small cell lung cancer (NSCLC) Metastasis 


Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Gang Liu
    • 1
  • Shengbao Xu
    • 2
  • Fanglei Jiao
    • 1
  • Tao Ren
    • 2
  • Qinchuan Li
    • 1
  1. 1.Department of Throatic Surgery, East HospitalTongji University School of MedicineShanghaiChina
  2. 2.Lung Cancer Center, East HospitalTongji University School of MedicineShanghaiChina

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