ADAM-12 as a diagnostic marker for the proliferation, migration and invasion in patients with small cell lung cancer

PLoS One. 2014 Jan 21;9(1):e85936. doi: 10.1371/journal.pone.0085936. eCollection 2014.


Small cell lung cancer (SCLC) is highly aggressive and is characterized by malignant metastasis. Approximately 90% of patients die due to extensive metastasis. The extracellular matrix (ECM) is a natural barrier that can prevent cellular invasion and metastasis. Therefore, degradation of the ECM must take place in order for extensive metastasis to occur. A disintegrin and metalloprotease (ADAM) is a multi-domain protease that plays an important role in tumorigenesis, as well as tumor development, invasion and metastasis. However, there have been few reports on the expression and role of ADAMs in SCLC. In the current study, the expression and role of ADAMs in SCLC proliferation, invasion and metastasis was investigated. A total of 150 SCLC tissue samples were examined by immunohistochemistry for ADAMs expression. ADAM-12 was found to be abundantly expressed in 72.67% samples and other ADAMs were found to be expressed in 10% to 40% of samples. ADAM-12 levels in serum and urine, from 70 SCLC patients and 40 normal controls, were also measured using ELISA. ADAM-12 expression was significantly higher in SCLC patients than in healthy controls and in patients with extensive disease compared to those with more limited disease. Silencing the expression of ADAM-12 in H1688 cells through the use of specific siRNA significantly reduced cellular proliferation, invasion and metastasis. Supplementing the expression of ADAM-12-L or -S in H345 cells, significantly enhanced cellular proliferation, invasion and metastasis. Animal models with metastatic SCLC also exhibited increased expression of ADAM-12 along with enhanced invasion and metastasis. In brief, ADAM-12 is an independent prognostic factor and diagnostic marker, and is involved in the proliferation, invasion and metastasis of SCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / blood
  • ADAM Proteins / metabolism*
  • ADAM Proteins / urine
  • ADAM12 Protein
  • Aged
  • Animals
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism*
  • Biomarkers, Tumor / urine
  • Cell Movement*
  • Cell Proliferation
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Male
  • Membrane Proteins / blood
  • Membrane Proteins / metabolism*
  • Membrane Proteins / urine
  • Mice
  • Mice, Nude
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis
  • Small Cell Lung Carcinoma / metabolism*
  • Small Cell Lung Carcinoma / pathology*
  • Up-Regulation


  • Biomarkers, Tumor
  • Membrane Proteins
  • ADAM Proteins
  • ADAM12 Protein
  • ADAM12 protein, human

Grants and funding

This work was supported by the National Natural Science Foundation of China (81302017). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.