An Experimental Study of Salivary Tumor Models in Mice

Abstract

Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed occurrence of distant lung metastases. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little is known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinomas in athymic nude mice. A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. The parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodules. The tumors were examined histopathologically for perineural invasion and regional or distant lung metastasis. We used an oral squamous cell carcinoma cell line as a control. Dr Jeffrey N. Myers (Department of Head and Neck surgery, University of Texas M.D. Anderson Cancer Center) kindly donated all cell lines. For this study, the exact logistic regression model was used to assess tumorigenicity and the effects of orthotopic (parotid) versus ectopic (subcutis) tumor development and metastases. The Ps for the location effect were evaluated against an a significance level of 0.05. n/a Implantation of tumor (melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 did not demonstrate significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland compared to the subcutis. By contrast, the mucosal squamous cell carcinoma cell line did not show significantly higher lung metastatic potential compared the subcutis. Perineural ACC tumor, from cells established in the parotid gland, needs further study. An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely mimics the clinical findings in human salivary ACC. This model should facilitate improved understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies for salivary ACC.