TY - JOUR
T1 - Induction of apoptosis in human neuroblastoma cells by abrogation of integrin-mediated cell adhesion
AU - Rozzo, Carla
AU - Chiesa, Valeria
AU - Caridi, Gianluca
AU - Pagnan, Gabriella
AU - Ponzoni, Mirco
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
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U2 - 10.1002/(SICI)1097-0215(19970317)70:6<688::AID-IJC11>3.0.CO;2-6
DO - 10.1002/(SICI)1097-0215(19970317)70:6<688::AID-IJC11>3.0.CO;2-6
M3 - Article
C2 - 9096651
AN - SCOPUS:0030990594
VL - 70
SP - 688
EP - 698
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 6
ER -