Inhibition of tumor growth by a truncated and soluble form of melanotransferrin

Exp Cell Res. 2007 Aug 1;313(13):2910-9. doi: 10.1016/j.yexcr.2007.04.013. Epub 2007 Apr 14.

Abstract

Melanotransferrin is a glycoprotein expressed at the cell membrane and secreted in the extracellular environment. Recombinant truncated form of membrane-bound melanotransferrin (sMTf) was reported to exert in vitro anti-angiogenic properties. Here we show that sMTf treatment leads to a 50% inhibition of neovascularization in Matrigel implants when stimulated by growth factors. Using a glioblastoma xenograft model, we demonstrate that sMTf delivery at 2.5 and 10 mg/kg/day by micro-osmotic pump inhibits tumor growth by 73% and 91%, respectively. In a lung carcinoma xenograft model, sMTf treatment at 2.5 and 10 mg/kg/day impeded tumor growth by 87% and 97%. Furthermore, subcutaneous glioblastoma and lung carcinoma tumors from mice treated with 10 mg/kg/day of sMTf present insignificant growth toward the study. In association with a reduction in endoglin mRNA expression, the hemoglobin content decreased by half in sMTf-treated glioblastoma tumors. In vitro experiments revealed that NCI-H460 cells treated with sMTf display an inhibition in their invasive capabilities with a concomitant reduction in the expression of the low-density lipoprotein receptor protein and urokinase plasminogen activator receptor. Altogether, our results demonstrate that sMTf exerts anti-cancer and anti-angiogenic activities, suggesting that its administration may provide novel therapeutic strategies for the treatment of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antigens, Neoplasm
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Fibroblast Growth Factors / antagonists & inhibitors
  • Fibroblast Growth Factors / pharmacology
  • Humans
  • Melanoma-Specific Antigens
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / pharmacology
  • Neoplasm Proteins / therapeutic use*
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Tissue Distribution
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • Vascular Endothelial Growth Factor A
  • fibroblast growth factor 13
  • Fibroblast Growth Factors