Preferential susceptibility of brain tumors to the antiangiogenic effects of an alpha(v) integrin antagonist.

Abstract

OBJECTIVE:

Brain tumors are highly angiogenic, and their growth and spread depend on the generation of new blood vessels. We examined the effect of the cyclic peptide antagonist pentapeptide EMD 121974, an antiangiogenic agent, on orthotopic and heterotopic brain tumor growth.

METHODS:

The human brain tumor cell lines DAOY (medulloblastoma) and U87 MG (glioblastoma) were injected into either the forebrain (orthotopic) or the subcutis (heterotopic) of nude mice, and daily systemic treatment with the active peptide was initiated after tumors were established.

RESULTS:

All control animals with orthotopic brain tumors and that received the inactive peptide EMD 135981 daily died as a result of tumor progression within 4 to 6 weeks; tumors measured 3 to 5 mm in diameter. In contrast, mice with orthotopic tumors that were treated daily with the active peptide survived for more than 16 weeks, and histological examination of the brains after 4, 8, and 12 weeks showed either no tumors or microscopic residual tumors. The growth of these brain tumor cells injected simultaneously or separately into the subcutis of nude mice (heterotopic model) was not affected by the active peptide, suggesting that the brain environment is a critical determinant of brain tumor susceptibility to growth inhibition by this pentapeptide.

CONCLUSION:

The cyclic pentapeptide EMD 121974 may become a treatment option specific to brain tumors. Because of its antiangiogenic effect, its use may be especially indicated after tumors are removed surgically.

• Authors: T J MacDonald, T Taga, H Shimada, P Tabrizi, B V Zlokovic, D A Cheresh, W E Laug
• Journal: Neurosurgery (Neurosurgery) Vol. 48 Issue 1 Pg. 151-7 (Jan 2001) ISSN: 0148-396X [Print] United States
• PMID: 11152340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Angiogenesis Inhibitors
• Integrins
• Peptides, Cyclic
• Snake Venoms
• Cilengitide

Topics

• Allantois (blood supply)
• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Blood Vessels (drug effects)
• Brain Neoplasms (drug therapy, pathology)
• Chick Embryo
• Chorion (blood supply)
• Drug Resistance
• Humans
• Integrins (antagonists & inhibitors)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Peptides, Cyclic (therapeutic use)
• Skin Neoplasms (drug therapy)
• Snake Venoms
• Transplantation, Heterologous