Tumor resistance to anti-VEGF therapy through up-regulation of VEGF-C expression

Dong Li1, Kun Xie1, Guitao Ding1

  • 1School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.

Cancer Letters
|December 17, 2013
PubMed

Insights

Tumors can become resistant to anti-VEGF cancer therapy by activating the VEGF-C pathway. Inhibiting VEGF-C can partially restore sensitivity to VEGF inhibitors, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Prolonged use of anti-vascular endothelial growth factor (VEGF) agents in cancer therapy can lead to tumor resistance.
  • Understanding the molecular mechanisms of this resistance is crucial for developing more effective treatments.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying resistance to anti-VEGF therapy.
  • To identify potential pathways involved in the development of resistance to VEGF inhibitors.

Main Methods:

  • Development of a VEGF inhibitor-resistant Lewis lung carcinoma (LLC) cell line through in vivo selection.
  • RNA-sequencing (RNA-seq) analysis to compare transcriptome profiles of resistant and non-resistant tumor cells.
  • Quantitative real-time PCR and immunohistochemical analyses to validate gene expression changes.

Main Results:

  • Vascular endothelial growth factor C (VEGF-C) was significantly up-regulated in resistant tumor cells compared to non-resistant cells.
  • Inhibition of VEGF-C in resistant cells suppressed endothelial cell migration in vitro.
  • Inhibition of VEGF-C partially restored the sensitivity of resistant cells to VEGF-Trap treatment in vivo.

Conclusions:

  • Tumors may develop resistance to anti-VEGF therapy by activating the VEGF-C pathway.
  • Targeting the VEGF-C pathway could be a strategy to overcome or prevent resistance to anti-VEGF cancer therapies.

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