An experimental study on establishment of highly metastasizing human adenoid cystic carcinoma line and treatment for metastasis

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Adenoid cystic carcinoma (ACC) is a rare malignant tumor occurring in the salivary gland, characterized by diffuse invasion and high frequency of lung metastasis, although the growth rate is very slow. The prognosis of patients with ACC depends upon the control of distant metastasis as well as local cure. However, the biologic behavior and possible treatment methods of ACC has not been well investigated because of a lack of an animal model of ACC. We attempted to establish in vivo metastasis model of ACC and to examine anticancer effect of some drugs in the experimental model. The following results were obtained;1.We established a human ACC line which is serially transplantable in nude mice and designated it as KOA-1. The KOA-1 tumor doubled in 9.3 days and retained the histological characteristics of a solid pattern of ACC even after 22 serial passages. Histological examination revealed that the KOA-1 tumor metastasised to the lung in about 17% of the mice at 3 months after subcutaneous transplantation.2.PCR analysis using human beta-globin gene showed a higher positive rate of metastasis ; 33% at 2 months and 50% at 3 months after subcutaneous transplantation.3.We further established a subline of KOA-1 by an in vivo selection method and named it KOA-1L3. The KOA-1L3 doubled in 1.3 days and metastasized to the lung within one week after subcutaneous transplantation.4.The tumor growth was suppressed in mice that received injection of 5FU and CDDP, while no anticancer effect was found after the injection of pirarubicin and doceraxel. The anticancer effect was superior when combined administration of CDDP and 5FU was done.