Squamous cell carcinoma of the head and neck affects 50,000 new cases in the United States each year. It is a debilitating and frequently disfiguring affliction that is in need of better treatment modalities. Recent studies of head and neck tumor biology have shown that proangiogenic and prometastatic cytokines work through transcription factors to contribute to the malignant phenotype of head and neck squamous cell carcinoma. This pilot projects aims to evaluate the effect of oral human recombinant lactoferrin as a chemotherapeutic agent on squamous cell carcinoma of the head and neck. Lactoferrin is a glycoprotein naturally found in breast milk with minimal demonstrable toxicity. It has been shown to exhibit antimicrobial activity and in more recent studies has been demonstrated to modulate the immune system and decrease growth and metastasis of certain malignant neoplasms. We hypothesize that oral administration of lactoferrin will decrease the growth of squamous cell carcinoma. We further posit that this effect on growth occurs through modulation of the immune system. Through a well-established murine model for floor of mouth squamous cell carcinoma, we will test our hypotheses by addressing the following specific aims: 1) To show that Lactoferrin inhibits the growth of head and neck tumor implants in the murine model. 2) To evaluate a dose-response relationship of oral Lactoferrin on head and neck cancer in the murine model. 3) To delineate the mechanism of action of lactoferrin with regard to influence on serum inflammatory cytokines, NF-kB activation, the cell cycle, and angiogenesis. Using human and murine tumors established in immunodeficient and immunocompetent mice, oral lactoferrin in three different doses will be administered via oral gavage for 10 days. The effects of lactoferrin on tumor growth, serum cytokine level, intratumoral cytokines, cell cycle, and the prometastatic transcription factor NF-kB activation will be evaluated. Identifying the effect and mechanism of lactoferrin on malignant tumors may allow further enhancement of its chemotherapeutic use, and may lead to improved therapies for head and neck squamous cell carcinoma.
| Wolf, Jeffrey S; Li, Guoyan; Varadhachary, Atul et al. (2007) Oral lactoferrin results in T cell-dependent tumor inhibition of head and neck squamous cell carcinoma in vivo. Clin Cancer Res 13:1601-10 |
