Zoledronic-acid-induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients

Gianluigi Ferretti, Alessandra Fabi, Paolo Carlini, Paola Papaldo, Paola Cordiali Fei, Serena Di Cosimo, Nello Salesi, Diana Giannarelli, Andrea Alimonti, Barbara Di Cocco, Giovanna D'Agosto, Valentina Bordignon, Elisabetta Trento, Francesco Cognetti

Research output: Contribution to journalArticle


Background: To evaluate the modifications of circulating angiogenic factors, metalloproteinases and acute-phase cytokines after the first single zoledronic acid (ZA) intravenous infusion. Experimental Design: Eighteen consecutive breast cancer patients with bone metastases were evaluated for circulating levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinase 1 (MMP-1), metalloproteinase 2 (MMP-2), interleukins 1β, 6 and 8 (IL-1β, IL-6, IL-8), interferon γ, tumor necrosis factor α (TNF-α) and transforming growth factor β1 just before and 2 and 7 days after ZA infusion. Results: The MMP-2 basal value showed a statistically significant decrease 48 h after ZA (p = 0.01), being at 7 days higher than the day 2 value (p = 0.03). The VEGF basal value showed a statistically significant decrease 48 h after ZA infusion (p = 0.03), increasing above the basal level at 7 days (p = 0.07). The bFGF basal level almost significantly decreased 2 days after infusion (p = 0.06), being at 7 days higher than the basal value (p = 0.09). Comparing the day 2 values with basal ones, the linear regression model showed a significant positive correlation between IL-8 and bFGF (p = 0.02), IL-8 and TNF-α (p <0.0001), bFGF and TNF-α (p = 0.01), MMP-1 and TNF-α (p = 0.02). Conclusions: ZA could exert an antiangiogenic activity and inhibition of tumor cell bone invasiveness by a transient reduction of VEGF, bFGF and MMP-2 circulating levels after infusion.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
Issue number1
Publication statusPublished - Aug 2005



  • Acute-phase cytokines
  • Bone metastases
  • Matrix metalloproteinase 2
  • Vascular endothelial growth factor
  • Zoledronate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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