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 ß-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.

Effect of a nitric oxide synthase inhibitor and a CXC chemokine receptor-4 antagonist on tumor growth and metastasis in a xenotransplanted mouse model of adenoid cystic carcinoma of the oral floor

“…This tumor is associated with spontaneous metastasis to the neck at the second passage level and the histological features change from ACC to undifferentiated carcinoma. The metastatic tumor, designated as ACCIM, shows a high frequency of spontaneous metastasis to the lung when transplanted subcutaneously in nude mice (24).…”

Silencing Id-1 with RNA Interference Inhibits Adenoid Cystic Carcinoma in Mice

“…Compared with other ACCM xenograft models [20], this one enabled direct visualization of tumor growth and invasion within viable tissues. Furthermore, orthotopic implantation is of particular importance with regard to the accurate preclinical evaluation of new antimetastatic agents [28].…”

“…Some research support that RNAi can be successfully applied to inhibit tumor development [20][21][22][23]. For therapeutic purposes, it is essential to introduce dsRNA inside the cells, so that they can recognize the target genes and cause their suppression, thereby preventing the disease.…”

Recapitulating orthotopic tumor model through establishment of a parotid gland tumor with lung metastasis using HeLa cell injection into nude mice

“…Tumor xenografts in nude mice seldom infiltrate and metastasis (1). Since an orthotopically grafted tumor shows more metastases than a heterotopically transplanted tumor, the orthotopic graft model has been used for the metastasis model (5,18).…”

“…Most current animal models consist of establishing subcutaneous tumors in athymic mice. However, subcutaneous tumors usually do not metastasize to regional lymph nodes or any distant site (1). Moreover, the organ microenvironment of the subcutis is certainly different from that of the organs where tumors originate.…”