title: Lactoferrin inhibits growth of malignant tumors of the head and neck.
abstract: Lactoferrin, a naturally occurring glycoprotein found in breast milk, has previously been shown to have antimicrobial properties and recently has been demonstrated to inhibit malignant tumor growth, presumably through immunomodulation. We hypothesized that intratumoral injection of human and murine recombinant lactoferrin would decrease the growth of malignant tumors in vivo. Using an orthotopic murine model for both squamous cell carcinoma and fibrosarcoma of the floor of the mouth, we administered lactoferrin directly into the tumors using variable dosing strategies. Additionally, we performed in vitro experiments to assess whether the effects of lactoferrin are due to direct cytotoxicity. Our results revealed growth inhibition of 50% (p=0.03)and 54% (p=0.01) as compared with controls for both human and murine tumor cells in immunodeficient and immunocompetent mice, respectively. There was a more dramatic effect in immunocompetent models which may identify immunomodulation as an important mechanism of action for lactoferrin. Support for immunomodulation as a possible mechanism was the lack of any difference between controls and the experimental groups in vitro. Lactoferrin proved effective in reducing malignant tumor growth in a murine model. These properties offer hope for its use as a primary or adjuvant chemotherapeutic agent. Further investigation focused on mechanism and delivery is needed.
authors.affiliation: Otolaryngology-Head and Neck Surgery, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. jwolf@smail.umaryland.edu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Wolf
authors.forename: Daqing
authors.initials: D
authors.lastname: Li
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Taylor
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007121:Immunocompetence; D015552:Injections, Intralesional; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D014407:Tumor Cells, Cultured
chemical_list: D007781:Lactoferrin