Advertisement

Tumor Biology

, Volume 31, Issue 3, pp 217–224 | Cite as

RNAi-mediated ADAM9 gene silencing inhibits metastasis of adenoid cystic carcinoma cells

Research Article

Abstract

A disintegrin and metalloproteinase 9 (ADAM9) is a type I transmembrane protein that has been associated with cancer development and metastases. Here, we show that ADAM9 is highly expressed in metastatic cancer tissues and in an adenoid cystic carcinoma cell line with a high metastatic potential. Using RNA interference for gene silencing, we show that ADAM9 is essential for in vitro cancer cell proliferation and invasion as well as in vivo cancer metastasis in an experimental murine model of lung metastases. These data indicate that ADAM9 is potentially an important new therapeutic target for the prevention of tumor metastases in adenoid cystic carcinoma.

Keywords

ADAM9 Adenoid cystic carcinoma Gene silencing Metalloproteinase Metastasis 

Abbreviations

ADAM

A disintegrin and metalloproteinase

ANOVA

analysis of variance

DMSO

dimethyl sulfoxide

EGFR

epidermal growth factor receptor

FBS

fetal bovine serum

FGFR

fibroblast growth factor receptor

GAPDH

glyceraldehyde-3-phosphate dehydrogenase

HB-EGF

heparin-binding EGF-like growth factor

qRT-PCR

quantitative real-time polymerase chain reaction

SPF

specific pathogen free

TGF

transforming growth factor

TNF

tumor necrosis factor

Notes

Acknowledgements

This work was supported by the Chinese National Natural Science Foundation of China (Grant Number 30600715), Shanghai Leading Academic Discipline Project (Project Number S30206), and projects of the Shanghai Science and Technology Committee (Project Number 08JC 1404800, 08JC 1414400).

References

  1. 1.
    Rapidis AD, Givalos N, Gakiopoulou H, Faratzis G, Stavrianos SD, Vilos GA, et al. Adenoid cystic carcinoma of the head and neck. Clinicopathological analysis of 23 patients and review of the literature. Oral Oncol. 2005;41:328–35.CrossRefPubMedGoogle Scholar
  2. 2.
    Hu K, Li SL, Gan YH, Wang CY, Yu GY. Epiregulin promotes migration and invasion of salivary adenoid cystic carcinoma cell line SACC-83 through activation of ERK and Akt. Oral Oncol. 2009;45:156–63.CrossRefPubMedGoogle Scholar
  3. 3.
    Becherer JD, Blobel CP. Biochemical properties and functions of membrane-anchored metallprotease-disintegrin proteins (ADAMs). Curr Top Dev Biol. 2003;54:101–23.CrossRefPubMedGoogle Scholar
  4. 4.
    Duffy MJ, McKiernan E, O'Donovan N, McGowan PM. Role of ADAMs in cancer formation and progression. Clin Cancer Res. 2009;15:1140–4.CrossRefPubMedGoogle Scholar
  5. 5.
    Rocks N, Paulissen G, El Hour M, Quesada F, Crahay C, Gueders M, et al. Emerging roles of ADAM and ADAMTS metalloproteinases in cancer. Biochimie. 2008;90:369–79.CrossRefPubMedGoogle Scholar
  6. 6.
    Peduto L, Reuter VE, Shaffer DR, Scher HI, Blobel CP. Critical function for ADAM9 in mouse prostate cancer. Cancer Res. 2005;65:9312–9.CrossRefPubMedGoogle Scholar
  7. 7.
    O’Shea C, McKie N, Buggy Y, Duggan C, Hill AD, McDermott E, et al. Expression of ADAM-9 mRNA and protein in human breast cancer. Int J Cancer. 2003;105:754–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Fritzsche FR, Jung M, Tölle A, et al. ADAM9 expression is a significant and independent prognostic marker of PSA relapse in prostate cancer. Eur Urol. 2008;54:1097–106.CrossRefPubMedGoogle Scholar
  9. 9.
    Huang D, Chen W, Zhang Z, Zhang P, He R, Zhou X, et al. Identification of genes with consistent expression alteration pattern in ACC-2 and ACC-M cells by cDNA array. Chin Med J (Engl). 2003;116:448–52.Google Scholar
  10. 10.
    Ikeda S, Fujimori M, Shibata S, et al. Combined immunohistochemistry of β-catenin, cytokeratin 7, and cytokeratin 20 is useful in discriminating primary lung adenocarcinomas from metastatic colorectal cancer. BMC Cancer. 2006;2:31.CrossRefGoogle Scholar
  11. 11.
    Xu Q, Zhang Z, Zhang P, Chen W. Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma. BMC Cancer. 2008;8:159.CrossRefPubMedGoogle Scholar
  12. 12.
    Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science. 2002;296:550–3.CrossRefPubMedGoogle Scholar
  13. 13.
    Cuneo KC, Fu A, Osusky KL, Geng L. Effects of vascular endothelial growth factor receptor inhibitor SU5416 and prostacyclin on murine lung metastasis. Anticancer Drugs. 2007;18:349–55.CrossRefPubMedGoogle Scholar
  14. 14.
    Chen J, Peng H, Ou-Yang X, He X. Research on the antitumor effect of ginsenoside Rg3 in B16 melanoma cells. Melanoma Res. 2008;18:322–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Nakashima Y, Yano M, Kobayashi Y, Moriyama S, Sasaki H, Toyama T, et al. Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery. Gene Ther. 2003;10:123–30.CrossRefPubMedGoogle Scholar
  16. 16.
    Carl-McGrath S, Lendeckel U, Ebert M, Roessner A, Röcken C. The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer. Int J Oncol. 2005;26:17–24.PubMedGoogle Scholar
  17. 17.
    Lendeckel U, Kohl J, Arndt M, Carl-McGrath S, Donat H, Röcken C. Increased expression of ADAM family members in human breast cancer and breast cancer cell lines. Cancer Res Clin Oncol. 2005;131:41–8.CrossRefGoogle Scholar
  18. 18.
    Zheng X, Jiang F, Katakowski M, et al. Inhibition of ADAM17 reduces hypoxia-induced brain tumor cell invasiveness. Cancer Sci. 2007;98:674–84.CrossRefPubMedGoogle Scholar
  19. 19.
    Rocks N, Estrella C, Paulissen G, et al. The metalloproteinase ADAM-12 regulates bronchial epithelial cell proliferation and apoptosis. Cell Prolif. 2008;41:988–1001.CrossRefPubMedGoogle Scholar
  20. 20.
    Ko SY, Lin SC, Wong YK, Liu CJ, Chang KW, Liu TY. Increase of disintergin metalloprotease 10(ADAM10) expression in oral squamous cell carcinoma. Cancer Lett. 2007;245:33–43.CrossRefPubMedGoogle Scholar
  21. 21.
    Fritzsche FR, Wassermann K, Jung M, Tölle A, Kristiansen I, Lein M, et al. ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression. BMC Cancer. 2008;8:179–87.CrossRefPubMedGoogle Scholar
  22. 22.
    Boelens MC, Kok K, Van der Vlies P, et al. Genomic aberrations in squamous cell lung carcinoma related to lymph node or distant metastasis. Lung Cancer. 2009;66:372–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Zigrino P, Mauch C, Fox JW, Nischt R. Adam-9 expression and regulation in human skin melanoma and melanoma cell lines. Int J Cancer. 2005;116:853–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Mazzocca A, Coppari R, De Franco R, Cho JY, Libermann TA, Pinzani M, et al. A secreted form of ADAM9 promotes carcinoma invasion through tumor-stromal interactions. Cancer Res. 2005;65:4728–38.CrossRefPubMedGoogle Scholar
  25. 25.
    Shintani Y, Higashiyama S, Ohta M, Hirabayashi H, Yamamoto S, Yoshimasu T, et al. Overexpression of ADAM9 in non-small cell lung cancer correlates with brain metastasis. Cancer Res. 2004;64:4190–6.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  1. 1.Department of Oral and Maxillofacial Surgery, Ninth People’s HospitalShanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of StomatologyShanghaiChina
  2. 2.Department of Dentistry, Zhongshan HospitalFudan UniversityShanghaiChina

Personalised recommendations