OPN-a Splicing Variant Expression in Non-small Cell Lung Cancer and its Effects on the Bone Metastatic Abilities of Lung Cancer Cells In Vitro

Anticancer Res. 2017 May;37(5):2245-2254. doi: 10.21873/anticanres.11561.

Abstract

Background: Osteopontin (OPN) is known to be involved in the development of certain cancers, including non-small cell lung cancer (NSCLC). However, its role in tumour progression remains unclear. The present study investigated the expression and biological impact of the OPN variant, OPN-a in NSCLC.

Materials and methods: OPN-a splicing variant expression in human NSCLC tissues was analyzed by real-time qPCR and immunohistochemistry (IHC), respectively. The impact of OPN-a on cellular functions of lung cancer cells was also evaluated. In addition, an in vitro model was developed for the assessment of interactions between lung cancer cells and bone tissue.

Results: The expression of OPN-a was higher in lung cancer tissues compared to normal controls. OPN-a promoted the malignant phenotypes of A549 cells by enhancing cell-adherent abilities to bone tissues, which could be mediated by the interaction with the cell surface receptor αvβ3 integrin.

Conclusion: OPN-a may represent a bone metastatic factor in human lung cancer, as well as a potential therapy target.

Keywords: Osteopontin; bone metastasis; lung cancer; splicing variant.

MeSH terms

  • A549 Cells
  • Alternative Splicing
  • Animals
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Femur / metabolism*
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Neoplasm Metastasis
  • Osteopontin / genetics
  • Osteopontin / metabolism*
  • Swine
  • Swine, Miniature

Substances

  • SPP1 protein, human
  • Osteopontin