Antisense to integrin alpha v inhibits growth and induces apoptosis in medulloblastoma cells.
BACKGROUND
Integrin alpha v promotes brain microvessel endothelium survival, yet its role in brain tumor cells is unknown.


METHODS
Alpha v synthesis in medulloblastoma cells Daoy, D341Med, and D283Med, was inhibited with antisense oligonucleotides (ASODN) to test the effect on growth and survivaL RESULTS: ASODN reduced alpha v surface expression 75% in a dose- and time-dependent manner (2 microM, 72 hours). Alpha v-deficient cells grown with vitronectin demonstrated reduced cell spreading, G0-G1 growth arrest, decreased proliferation and increased apoptosis compared to controls or alpha v-deficient cells grown with collagen. Furthermore, insulin-like growth factor-I (IGF-I) suboptimally stimulated proliferation and survival of alpha v-deficient cells, suggesting that alpha v-IGF-I interactions potentiate medulloblastoma growth. Finally, treatment with alpha v-blocking antibody induced caspase-8 and caspase-3 expression, while apoptosis of alpha v-deficient cells was associated only with increased caspase-3.


CONCLUSIONS
Alpha v integrin supports medulloblastoma growth by activating adhesion-dependent and -independent survival pathways and thus may serve as a novel therapeutic target in this tumor.
MacDonald
T J
TJ
Children's Research Institute, Center for Cancer and Transplantation Biology, Children's National Medical Center, The George Washington University School of Medicine, Washington, DC 20010, USA. tmcdona@cnmc.org
Ladisch
S
S
D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D039564:Integrin alphaV; D008527:Medulloblastoma / Q000378:metabolism* / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D006131:Growth Inhibitors; D039564:Integrin alphaV; D016376:Oligonucleotides, Antisense