期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 10, 页码 3939-3944出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0712366105
关键词
anti-angiogenic; cancer; CRF; peptide; CRFR2
The corticotropin-releasing factor (CRF) receptor CRFR2 is expressed widely in peripheral tissues and in the vasculature, although its functional roles in those tissues have only recently begun to be elucidated. Previously we found that genetic deletion of CRFR2 resulted in profound postnatal hypervascularization in mice, characterized by both an increase in total vessel number and a dramatic increase in vessel diameter. These data strongly suggested that ligands for CRFR2 act to limit tissue vascularity, perhaps as a counterbalance to factors that promote neovascularization. Urocortin 2 (Ucn2) is a specific ligand for the CRFR2. We hypothesized that activation of CRFR2 by Ucn2 might thus suppress tumor vascularization and consequently limit tumor growth. Here, we show that viral-mediated expression of Ucn2 strikingly inhibits the growth and vascularization of Lewis Lung Carcinoma Cell (LLCC) tumors in vivo. Further, we found that this effect on tumor growth inhibition was independent of whether exposure to Ucn2 occurred before or after establishment of measurable tumors. In vitro, Ucn2 directly inhibited the proliferation of LLCC, suggesting that the tumor-suppressing effects of CRFR2 activation involve a dual mechanism of both a direct inhibition of tumor cell cycling and the suppression of tumor vascularization. These results establish that Ucn2 inhibits tumor growth, suggesting a potential therapeutic role for CRFR2 ligands in clinical malignancies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据