Decreased B16F10 melanoma growth and impaired vascularization in telomerase-deficient mice with critically short telomeres.
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.
Franco
Sonia
S
Department of Immunology and Oncology, National Centre of Biotechnology, Madrid 28049, Spain.
Segura
Inmaculada
I
Riese
Hans H
HH
Blasco
María A
MA
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D007797:Laminin; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000473:pathology; D011509:Proteoglycans; D019098:Telomerase / Q000172:deficiency* / Q000235:genetics; D016615:Telomere / Q000502:physiology*
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D019098:Telomerase