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

AbstractBACKGROUND:
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. 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.
METHODS:
Immunohistochemistry 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.
RESULTS:
It 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.
CONCLUSIONS:
These 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.
AuthorsQin Xu, Xiuming Liu, Wantao Chen, Zhiyuan Zhang
JournalJournal of translational medicine (J Transl Med) Vol. 8 Pg. 136 (Dec 20 2010) ISSN: 1479-5876 [Electronic] England
PMID21171968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Membrane Proteins
  • RNA, Messenger
  • Amyloid Precursor Protein Secretases
  • ADAM Proteins
  • ADAM10 Protein
  • ADAM10 protein, human
Topics
  • ADAM Proteins (genetics, metabolism)
  • ADAM10 Protein
  • Amyloid Precursor Protein Secretases (genetics, metabolism)
  • Animals
  • Carcinoma, Adenoid Cystic (enzymology, genetics, pathology)
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Membrane Proteins (genetics, metabolism)
  • Mice
  • Neoplasm Metastasis
  • RNA Interference
  • RNA, Messenger (genetics, metabolism)

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