PIVL, a snake venom Kunitz-type serine protease inhibitor, inhibits in vitro and in vivo angiogenesis.

authors

  • Morjen Maram
  • Honoré Stéphane
  • Bazaa Amine
  • Abdelkafi-Koubaa Zaineb
  • Ellafi Ameneallah
  • Mabrouk Kamel
  • Kovacic Hervé
  • El Ayeb Mohamed
  • Marrakchi Naziha
  • Luis José

keywords

  • Chorioallantoic membrane assay
  • Angiogenesis
  • Integrin
  • Microtubule dynamics
  • Migration

document type

ART

abstract

: Development and homeostasis of the vascular system requires integrin-promoting endothelial cell adhesion, migration and survival. Nowadays, integrins represent potential targets for pharmacological agents and open new avenues for the control of metastatic spread in the treatment of tumor malignancies. We have already reported that PIVL, a serine protease inhibitor isolated from Macrovipera lebetina venom, displays an anti-tumor effect through the interference with integrin receptor function. Here, we report that PIVL inhibits human vascular endothelial cell adhesion and migration onto fibrinogen and fibronectin in a dose-dependent manner without any cytotoxicity. Furthermore, we show that PIVL increases microtubule dynamic instability in HMEC-1 transfected with EGFP-tagged α-tubulin. Using Matrigel™ and chick chorioallantoic membrane assays, we demonstrate that PIVL exhibits a strong anti-angiogenic effect both in vitro and in vivo. Interestingly, results herein reveal that the potent anti-angiogenic properties of PIVL are mediated by its RGD-like motif ((41)RGN(43)).

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