Fas/FasL interaction of nucleus pulposus and cancer cells with the activation of caspases

Abstract

Spinal metastatic disease is characterised by the preservation of the intervertebral disc structure, even after severe destruction of the vertebral body by neoplastic tissues. Anatomical features of the discs are thought to be the reason for the disc's resistance to metastatic cancer. However, little is known about the biochemical mechanism to prevent or attenuate the local invasion of cancer cells into the discs. The purpose of this study was to investigate the hypothesis that Fas ligand (FasL) produced by nucleus pulposus cells can kill Fas-expressing cancer cells infiltrating into the discs by the activation of caspases. Fas-expressing MCF-7 breast cancer cells were cultured with (experimental group) and without (control group) supernatant of nucleus pulposus cells containing FasL (50 pg/ml) for 48 h. The apoptosis of MCF-7 breast cancer cells was determined by the TUNEL technique. In addition, the activation of caspase-8, -9 and -3 was investigated by Western blot analysis. After treatment with supernatant of the nucleus pulposus cells containing FasL, the apoptosis of MCF-7 breast cancer cells was significantly increased, along with the activation of caspase-8, -9 and -3 compared with those of the control group. Our results suggest that the Fas/FasL interaction of nucleus pulposus and cancer cells might be a potential mechanism of the disc's resistance to metastatic cancer.