Induction of apoptosis in human neuroblastoma cells by abrogation of integrin-mediated cell adhesion

✍ Scribed by Carla Rozzo; Valeria Chiesa; Gianluca Caridi; Gabriella Pagnan; Mirco Ponzoni

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 396 KB
• Volume: 70
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970317)70:6<688::aid-ijc11>3.0.co;2-6

✦ Synopsis

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 NB cell lines which represent different stages of neuronal maturation. Retinoic acid (RA) had different effects on the 2 NB 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 GI-LI-N cells. These findings were also obtained by treating both NB cell lines with the apoptotic agent fenretinide. Furthermore, treatment of NB cells with anti-sense oligonucleotides to b 1 integrin chain specifically induced chromatin condensation and nucleosomal DNA laddering. Moreover, blocking cell-matrix interactions by means of perturbing antibody against b 1 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.