Cancer Research Cell Death Mechanisms and Cancer Therapy Telomeres
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[Cancer Research 62, 552-559, January 15, 2002]
© 2002 American Association for Cancer Research

Molecular Biology and Genetics

Decreased B16F10 Melanoma Growth and Impaired Vascularization in Telomerase-deficient Mice with Critically Short Telomeres1

Sonia Franco, Inmaculada Segura, Hans H. Riese and María A. Blasco2

Department of Immunology and Oncology, National Centre of Biotechnology, Madrid 28049, Spain

Endothelial cell function and angiogenesis are modulated by aging. However, the underlying molecular mechanisms are largely unknown. Here we show that in telomerase-deficient mice Terc-/-, short telomeres result in a sharp decrease in angiogenesis in both Matrigel implants and murine melanoma grafts. In the latter model, decreased microvessel counts in late generation Terc-/- mice led to diminished tumor cell proliferation and increased tumor cell apoptosis, resulting in a lower tumor growth rate. Our results indicate that telomere length is a key molecular determinant of angiogenic potential in vivo and that telomere length modifiers and telomerase inhibitors could be useful antiangiogenic agents.




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Copyright © 2002 by the American Association for Cancer Research.