Inhibition of tumor growth by a truncated and soluble form of melanotransferrin.
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.
Rolland
Yannève
Y
Laboratoire de Médecine Moléculaire, Service d'Hémato-Oncologie, Hôpital Ste-Justine - Université du Québec à Montréal, Succursale Centre-ville, Montréal, Québec, Canada.
Demeule
Michel
M
Michaud-Levesque
Jonathan
J
Béliveau
Richard
R
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D058950:Melanoma-Specific Antigens; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors