Establishment of nude mouse transplantable model of a human adenoid cystic carcinoma of the oral floor showing metastasis to the lymph node and lung

Abstract

Adenoid cystic carcinoma (ACC) is a generally slow-growing but highly malignant salivary gland neoplasm with remarkable capacities for local invasion and lung metastasis. The precise characteristics of ACC are not fully understood because there was no suitable animal model. We have successfully established a new human tumor line (ACCI) derived from ACC of the oral floor, which showed a cribriform pattern histologically and serially transplantable into nude mice. This tumor developed spontaneous metastasis to the neck at the second passage level, and the histological feature changed from ACC to undifferentiated carcinoma (ACCIM). ACCIM caused spontaneous metastasis to the lung at high incidence when transplanted subcutaneously in nude mice. In this study, we examined the characteristics of this interesting human ACC metastatic line. Tumor fragments were subcutaneously transplanted into nude mice and tumor growth was measured at 1-week intervals. Histological and immunohistochemical examinations were performed. As a result, the tumor growth rate of ACCIM increased as compared to that of ACCI, and the PCNA labeling index was elevated. Furthermore, ACCIM produced multiple metastases to lymph nodes and lungs 5 months after transplantation, and all mice died within 6 months. These multiple metastases were also confirmed in orthotopic transplantation to the tongue. RT-PCR analysis revealed that ACCIM expressed human beta-actin, indicating its human origin. From these findings, ACCIM transplanted into nude mice would provide a useful model for investigating the biological behaviour of ACC.