Advertisement

Tumor Biology

, Volume 37, Issue 7, pp 8681–8689 | Cite as

Overexpression of ADAMTS5 can regulate the migration and invasion of non-small cell lung cancer

  • Jun Gu
  • Jie Chen
  • Jian Feng
  • Yifei Liu
  • Qun Xue
  • Guoxin Mao
  • Ling Gai
  • Xiaoning Lu
  • Rui Zhang
  • Jialin Cheng
  • Yanxia Hu
  • Mengting Shao
  • Hong Shen
  • Jianan Huang
Original Article

Abstract

Non-small cell lung cancer (NSCLC) is the major cause of cancer-related lethality among human cancer patients globally, and the poor prognosis of this cancer is mainly explained by metastasis, so it is essential to find out the molecule mechanisms and a novel therapeutic for NSCLC. A disintegrin and metalloprotease with thrombospondin motif 5 (ADAMTS5) belongs to the protease family. It has been reported to participate in tumor migration and invasion. In this study, we showed that the expression of ADAMTS5 was higher in lung cancer tissues by Western blot. The immunohistochemistry analysis was performed in 140 NSCLC cases, and the result indicated that ADAMTS5 was significantly associated with clinical pathologic variables. The Kaplan–Meier curve showed that the high expression of ADAMTS5 was related to poor prognosis of lung cancer patients. Wound healing assays and transwell migration assays revealed that the high expression of ADAMTS5 promoted the migration and invasion of NSCLC. In a word, our findings suggest that ADAMTS5 can regulate the migration and invasion of NSCLC and it may be a useful target of therapy in NSCLC.

Keywords

ADAMTS5 Non-small cell lung cancer Migration Invasion 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 31270940) the Natural Science Foundation of Jiangsu Province (no. BK2012606) and Clinical Key Speciality Project of China.

Compliance with ethical standards

Conflicts of interest

None

References

  1. 1.
    Bender E. Epidemiology: the dominant malignancy. Nature. 2014;513(7517):S2–3.CrossRefPubMedGoogle Scholar
  2. 2.
    Ji L et al. Nrf2 pathway regulates multidrug-resistance-associated protein 1 in small cell lung cancer. PLoS One. 2013;8(5), e63404.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Arola J et al. p53 and Ki67 in adrenocortical tumors. Endocr Res. 2000;26(4):861–5.CrossRefPubMedGoogle Scholar
  4. 4.
    Siegel R et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.CrossRefPubMedGoogle Scholar
  5. 5.
    Liu SV, Giaccone G. Lung cancer in 2013: refining standard practice and admitting uncertainty. Nat Rev Clin Oncol. 2014;11(2):69–70.CrossRefPubMedGoogle Scholar
  6. 6.
    Gupta GP, Massague J. Cancer metastasis: building a framework. Cell. 2006;127(4):679–95.CrossRefPubMedGoogle Scholar
  7. 7.
    Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer. 2009;9(4):239–52.CrossRefPubMedGoogle Scholar
  8. 8.
    Barney LE et al. A cell-ECM screening method to predict breast cancer metastasis. Integr Biol (Camb). 2015;7(2):198–212.CrossRefGoogle Scholar
  9. 9.
    Parsons JT, Horwitz AR, Schwartz MA. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol. 2010;11(9):633–43.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Sung SY et al. Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance. Curr Probl Cancer. 2007;31(2):36–100.CrossRefPubMedGoogle Scholar
  11. 11.
    Friedl P, Wolf K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003;3(5):362–74.CrossRefPubMedGoogle Scholar
  12. 12.
    Hoshino D et al. The phosphoinositide-binding protein ZF21 regulates ECM degradation by invadopodia. PLoS One. 2013;8(1), e50825.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ohtsuka T et al. ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis. Int J Cancer. 2006;118(2):263–73.CrossRefPubMedGoogle Scholar
  14. 14.
    Arribas J, Bech-Serra JJ, Santiago-Josefat B. ADAMs, cell migration and cancer. Cancer Metastasis Rev. 2006;25(1):57–68.CrossRefPubMedGoogle Scholar
  15. 15.
    Shao S et al. ADAM-12 as a diagnostic marker for the proliferation, migration and invasion in patients with small cell lung cancer. PLoS One. 2014;9(1), e85936.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ishikawa N et al. ADAM8 as a novel serological and histochemical marker for lung cancer. Clin Cancer Res. 2004;10(24):8363–70.CrossRefPubMedGoogle Scholar
  17. 17.
    Schutz A et al. Expression of ADAM15 in lung carcinomas. Virchows Arch. 2005;446(4):421–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Rocks N et al. Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC). Br J Cancer. 2006;94(5):724–30.PubMedPubMedCentralGoogle Scholar
  19. 19.
    O’Shea C et al. Expression of ADAM-9 mRNA and protein in human breast cancer. Int J Cancer. 2003;105(6):754–61.CrossRefPubMedGoogle Scholar
  20. 20.
    Kveiborg M et al. A role for ADAM12 in breast tumor progression and stromal cell apoptosis. Cancer Res. 2005;65(11):4754–61.CrossRefPubMedGoogle Scholar
  21. 21.
    Lei Y et al. Interaction of LHBs with C53 promotes hepatocyte mitotic entry: a novel mechanism for HBV-induced hepatocellular carcinoma. Oncol Rep. 2012;27(1):151–9.PubMedGoogle Scholar
  22. 22.
    Nakada M et al. Human glioblastomas overexpress ADAMTS-5 that degrades brevican. Acta Neuropathol. 2005;110(3):239–46.CrossRefPubMedGoogle Scholar
  23. 23.
    Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141(1):52–67.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Wood SL et al. The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev. 2014;40(4):558–66.CrossRefPubMedGoogle Scholar
  25. 25.
    Mochizuki S, Okada Y. ADAMs in cancer cell proliferation and progression. Cancer Sci. 2007;98(5):621–8.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Jun Gu
    • 1
    • 3
  • Jie Chen
    • 2
    • 6
  • Jian Feng
    • 3
  • Yifei Liu
    • 4
  • Qun Xue
    • 5
  • Guoxin Mao
    • 6
  • Ling Gai
    • 6
  • Xiaoning Lu
    • 5
  • Rui Zhang
    • 3
  • Jialin Cheng
    • 6
  • Yanxia Hu
    • 3
  • Mengting Shao
    • 6
  • Hong Shen
    • 6
  • Jianan Huang
    • 1
  1. 1.Department of RespiratoryThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  2. 2.Department of OncologyJiangyin People’s HospitalJiangyinChina
  3. 3.Department of RespiratoryAffiliated Hospital of Nantong UniversityNantongChina
  4. 4.Department of PathologyAffiliated Hospital of Nantong UniversityNantongChina
  5. 5.Department of Thoracic SurgeryAffiliated Hospital of Nantong UniversityNantongChina
  6. 6.Department of OncologyAffiliated Hospital of Nantong UniversityNantongChina

Personalised recommendations