Inhibiting adenoid cystic carcinoma cells growth and metastasis by blocking the expression of ADAM 10 using RNA interference

Qin Xu,Xiuming Liu,Zhiyuan Zhang,Wantao Chen

doi:10.1186/1479-5876-8-136

Abstract

BackgroundAdenoid cystic carcinoma is one of the most common types of salivary gland cancers. The poor long-term prognosis for patients with adenoid cystic carcinoma is mainly due to local recurrence and distant metastasis. Disintegrin and metalloprotease 10 (ADAM 10) is a transmembrane protein associated with metastasis in a number of diverse of cancers. The aim of this study was to analyze the relationship between ADAM 10 and the invasive and metastatic potentials as well as the proliferation capability of adenoid cystic carcinoma cells in vitro and in vivo.MethodsImmunohistochemistry and Western blot analysis were applied to detect ADAM 10 expression levels in metastatic cancer tissues, corresponding primary adenoid cystic carcinoma tissues, adenoid cystic carcinoma cell lines with high metastatic potential, and adenoid cystic carcinoma cell lines with low metastatic potential. RNA interference was used to knockdown ADAM 10 expression in adenoid cystic carcinoma cell lines with high metastatic potential. Furthermore, the invasive and metastatic potentials as well as the proliferation capability of the treated cells were observed in vitro and in vivo.ResultsIt was observed that ADAM 10 was expressed at a significantly higher level in metastatic cancer tissues and in adenoid cystic carcinoma cell lines with high metastatic potential than in corresponding primary adenoid cystic carcinomas and adenoid cystic carcinoma cell lines with low metastatic potential. Additionally, silencing of ADAM 10 resulted in inhibition of cell growth and invasion in vitro as well as inhibition of cancer metastasis in an experimental murine model of lung metastases in vivo.ConclusionsThese studies suggested that ADAM 10 plays an important role in regulating proliferation and metastasis of adenoid cystic carcinoma cells. ADAM 10 is potentially an important therapeutic target for the prevention of tumor metastases in adenoid cystic carcinoma.

Highlights

Adenoid cystic carcinoma is one of the most common types of salivary gland cancers
The poor long-term prognosis for patients with adenoid cystic carcinoma is mainly due to local recurrence related to perineural invasion and delayed onset of distant metastasis, to the lungs [1,2]
ADAM 10 expression in primary and metastasized adenoid cystic carcinoma tissue samples First, ADAM 10 expression was examined by immunostaining of 15 paired tissues from patients with oral adenoid cystic carcinoma and cervical lymph node metastasis

Summary

Introduction

Adenoid cystic carcinoma is one of the most common types of salivary gland cancers. The poor long-term prognosis for patients with adenoid cystic carcinoma is mainly due to local recurrence and distant metastasis. The poor long-term prognosis for patients with adenoid cystic carcinoma is mainly due to local recurrence related to perineural invasion and delayed onset of distant metastasis, to the lungs [1,2]. The ADAM (A disintegrin and metalloprotease) family is a class of type I transmembrane proteins that participate in a wide range of physiological functions. Our previous study found that ADAM 10 expression in adenoid cystic carcinoma cells with high metastatic potential was significantly higher than that in adenoid cystic carcinoma cells with low metastatic potential based on gene chip analysis [10] These findings strongly suggest that ADAM 10 plays an essential role in tumor metastases

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