An Experimental Study for Establishment of Orthotopic Salivary Tumor Models in Mice

PURPOSE: 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 onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. EXPERIMENTAL DESIGN: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A 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 nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. RESULTS: 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 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn't show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. CONCLUSION: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

AN IMMUNOHISTOCHEMICAL STUDY ON PROLIFERATION, DIFFERENTIATION, AND APOPTOSIS IN THE EPITHELIAL CELLS OF THE ODONTOGENIC CYSTS

The epithelium of odontogenic cyst seems to be in a specific status of cellular proliferation and cytodifferentiation. With the identification of various genes, which play essential roles in the specific stages of cellular proliferation and differentiation, the cellular conditions of odontogenic cyst epithelium need to be reevaluated. This study aimed to estimate the degree of proliferating, differentiating and apoptotic activities of odontogenic cyst epithelium using antisera of PCNA, Ki-67, MPM-2, transglutaminase C, heat shock protein 70 and ApopTag method in 19 cases of odontogenic cysts. Cellular changes of the cyst epithelium were measured by intensity of each immunohistochemical staining. Results were as follows: 1. The proliferating activity of the cyst epithelium was slightly lower than that of normal oral mucosal epithelium, with the use of primary antibodies against PCNA, Ki-67, and MPM-2. And the proliferating activity of the epithelium in OKC group was even higher than that of the epithelium in non-OKC group. 2. The odontogenic cysts showed weakly positive reaction with transglutaminase C, but strongly positive reaction with HSP 70. 3. Occasionally, only a few apoptotic cell was observed in the superficial keratin layer of OKC. 4. The hyperplastic cyst epithelium infiltrated with mild inflammatory cells showed diffusely positive reaction with different proliferating factors. From the above results, we presumed that the endogenous proliferating and differentiating activity of the cyst epithelium was slightly lower than that of normal oral mucosal epithelium, and also supposed that the cyst epithelium could be reactivated for the further proliferation by the exogenous factors, such as inflammatory reaction and any chemicophysical irritations.