The survival, proliferation and differentiation of neuroblastoma (NB) cells are largely dependent on adhesion to extracellular matrix (ECM) proteins. Integrin occupancy seems to play a primary role. To elucidate the role of integrin heterodimers during neuronal cell death, we have analysed the changes in integrin expression in 2 human NE cell lines which represent different stages of neuronal maturation. Retinoic acid (RA) had different effects on the 2 NE cell lines: on LAN-5 cells it acted as a differentiation-promoting agent, while it had an anti-proliferative effect on GI-LI-N cells, driving them to apoptosis. Indeed, this occurrence was evidenced by the visualization of a 'DNA ladder' on gel electrophoresis, by propidium iodide staining, and by DNA flow cytofluorimetric analysis. RA treatment rapidly and drastically decreased integrin expression and cell adhesion on CI-LI-N cells. These findings were also obtained by treating both NE cell lines with the apoptotic agent fenretinide. Furthermore, treatment of NE cells with anti-sense oligonucleotides to β1 integrin chain specifically induced chromatin condensation and nucleosomal DNA laddering. Moreover, blocking cell-matrix interactions by means of perturbing antibody against β1 subunit resulted in the induction of typical features of apoptotic cells. In conclusion, these findings indicate that abrogation of cell adhesion through down-modulation of integrin receptors plays a crucial role in the induction of neuroblastoma programmed cell death.
|Number of pages||11|
|Journal||International Journal of Cancer|
|Publication status||Published - 1997|
ASJC Scopus subject areas
- Cancer Research