Changes of histological and biological features by serial passages in a human adenoid cystic carcinoma line transplantable in nude mice

The basic histologic patterns of adenoid cystic carcinoma (ACC) are classified into three types (tubular, cribriform and solid), but clinical significance of the histological type is unclear. We have successfully established a human tumor line derived from ACC that is serially transplantable in nude mice. This tumor showed an increased growth rate as the passage levels proceeded, and the histological type was changed from a cribriform pattern in the initial stage to a solid one. In this study, we investigated the relationship between histological type and biological characteristics by analyzing the serially transplantable ACC tumor model. As a result, the tumor growth rate at the 15th passage level was increased approximately 5-fold compared with that at the initial passage level. In the histological type, approximately 30% of the cribriform pattern in the initial level was changed to a solid one at the 15th passage level, and the PCNA labeling index was elevated 4-fold. Concomitant with this, expression of Ki-67, p53 and bcl-2 proteins was increased, and apoptotic cells were decreased as demonstrated by the TUNEL method. From these findings, it was suggested that cell proliferation and histological change of this ACC tumor are related to the inhibition of apoptosis. This tumor line would provide a useful model for investigating the biological behavior of ACC.