Vinblastine inhibits the angiogenic response induced by adrenomedullin in vitro and in vivo

Domenico Ribatti, Diego Guidolin, Maria Teresa Conconi, Beatrice Nico, Silvia Baiguera, Pier Paolo Parnigotto, Angelo Vacca, Gastone Giovanni Nussdorfer

Research output: Contribution to journalArticlepeer-review

Abstract

Adrenomedullin (ADM) is protumorigenic by stimulating tumor cell growth and angiogenesis. In this context, ADM is identified as a novel target for antiangiogenic therapy. In this study, we addressed the possibility that vinblastine (VBL), as demonstrated in other experimental conditions, may act as an angiostatic molecule in the angiogenic response induced by ADM in two assays, such as Matrigel tube formation in vitro and angiogenesis in the chick embryo chorioallantoic membrane (CAM) in vivo. When tested on Matrigel, ADM caused a morphogenetic effect. In fact, endothelial cells spread and aligned with each other to form branching anastomosing tubes with multicentric junctions that gave rise to a meshwork of capillary-like structures. When ADM was administered in the presence of VBL, the capillary-like tubes were interrupted, most cells were spherical, either isolated or aggregated in small clumps. In the CAM assay, ADM induced a strong angiogenic response, which was counter-acted by the treatment with VBL. Overall, these observations implicate ADM as a promoter of tumor growth and a possible target for anticancer strategies, such as the use of VBL at very low, nontoxic doses. Nevertheless, the antiangiogenic acitivity of low-dose VBL deserves further investigation, alone or together with other antiangiogenic agents for the treatment of tumors characterized by enhanced angiogenesis.

Original languageEnglish
Pages (from-to)6458-6461
Number of pages4
JournalOncogene
Volume22
Issue number41
DOIs
Publication statusPublished - Sep 25 2003

Keywords

  • Adrenomedullin
  • Angiogenesis
  • Antiangiogenesis
  • Chorioallantoic membrane
  • Matrigel
  • Vinblastine

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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