Halofuginone inhibits angiogenesis and growth in implanted metastatic rat brain tumor model - An MRI study

Rinat Abramovitch, Anna Itzik, Hila Harel, Arnon Nagler, Israel Vlodavsky, Tali Siegal

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific anglogenic inhibitors. Halofuginone (HF) is a potent inhibitor of collagen type α1(I). In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI), we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001). Treatment with HF significantly prolonged survival of treated animals (142%; P = .001). In HF-treated rats, tumor vascularteation was inhibited by 30% on day 13 and by 37% on day 19 (P < .05). Additionally, HF treatment inhibited vessel maturation (P = .03). Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.

Original languageEnglish
Pages (from-to)480-489
Number of pages10
JournalNeoplasia
Volume6
Issue number5
DOIs
StatePublished - 2004
Externally publishedYes

Keywords

  • Angiogenesis
  • Brain tumor
  • Halofuginone
  • MRI
  • Vessel cooption

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