Antisense to integrin alpha v inhibits growth and induces apoptosis in medulloblastoma cells

Anticancer Res. Nov-Dec 2001;21(6A):3785-91.

Abstract

Background: Integrin alpha v promotes brain microvessel endothelium survival, yet its role in brain tumor cells is unknown.

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Growth Inhibitors / pharmacology
  • Humans
  • Integrin alphaV
  • Medulloblastoma / metabolism*
  • Medulloblastoma / pathology*
  • Oligonucleotides, Antisense / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • Growth Inhibitors
  • Integrin alphaV
  • Oligonucleotides, Antisense