Decreased B16F10 melanoma growth and impaired vascularization in telomerase-deficient mice with critically short telomeres.

Abstract

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.