Μolecular impact of bone morphogenetic protein 7, on lung cancer cells and its clinical significance

Int J Mol Med. 2012 Jun;29(6):1016-24. doi: 10.3892/ijmm.2012.948. Epub 2012 Mar 23.

Abstract

The aim of this study was to investigate the expression of bone morphogenetic protein 7 (BMP7), in human pulmonary cancer tissues/cells and to evaluate the cellular impact of bone morphogenetic proteins on pulmonary cancer cells. BMP7 expression was determined in human lung cancer cell lines. The invasiveness and growth of cells transfected with BMP7, in vitro, were evaluated using the in vitro invasion assay and in vitro tumour models. Cellular migration was analysed using wounding assays. BMP7-positive tumours correlated with the absence of bone metastasis (P=0.040). In this analysis, we identified that 4 of 4 small cell lung cancer (SCLC) tissue specimens had no BMP7 expression, which illustrated that BMP7 may have no role in SCLC. BMP7 expression was not correlated with the overall survival time in lung cancer patients. Downregulation of BMP7 expression significantly inhibited the invasiveness of SPC-A1 cells (P<0.001) and forced-expression of BMP7 dramatically increased the motility of A549 cells. Overexpression of BMP7 in A549 cells and its knockdown in SPC-A1 cells did not significantly alter proliferation compared with the control cells (P>0.5 respectively). In conclusion, we have demonstrated that BMP7 has an important role in controlling lung cancer cell motility and invasiveness, without affecting the growth process, cell proliferation and cell apoptosis. A higher BMP7 expression may be an indicator for bone metastasis. The therapeutic role of BMP7 warrants further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 7 / genetics*
  • Bone Morphogenetic Protein 7 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cohort Studies
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Small Interfering / metabolism
  • Staining and Labeling
  • Tetracycline / pharmacology
  • Time Factors
  • Tumor Stem Cell Assay
  • Wound Healing / drug effects

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • RNA, Small Interfering
  • Tetracycline