Franco Sonia, Segura Inmaculada, Riese Hans H, Blasco María A
Department of Immunology and Oncology, National Centre of Biotechnology, Madrid 28049, Spain.
Cancer Res. 2002 Jan 15;62(2):552-9.
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.
内皮细胞功能和血管生成受衰老调节。然而，其潜在的分子机制大多未知。在此我们表明，在端粒酶缺陷型小鼠Terc(-/-)中，短端粒导致基质胶植入物和小鼠黑色素瘤移植瘤中的血管生成急剧减少。在后一种模型中，晚期Terc(-/-)小鼠微血管数量减少导致肿瘤细胞增殖减少和肿瘤细胞凋亡增加，从而使肿瘤生长速率降低。我们的结果表明，端粒长度是体内血管生成潜力的关键分子决定因素，端粒长度调节剂和端粒酶抑制剂可能是有用的抗血管生成药物。
