Hormones & Cancer Division, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.
Cancer Lett. 2012 Apr 1;317(1):41-8. doi: 10.1016/j.canlet.2011.11.011. Epub 2011 Nov 13.
Cell migration and invasion leading to metastasis is a major cause of death from endometrial cancer (EC). We have shown that the rate of EC cell migration is inversely related to the level of insulin-like growth factor protein-3 (IGFBP-3). Down-regulation of IGFBP-3 by siRNA in EC cells accelerated migration without affecting proliferation and cells displayed a more migratory phenotype, with co-localization of migration-associated markers at the leading edge of cell membranes. Opposite effects were seen with either the addition of recombinant IGFBP-3 or overexpression of IGFBP-3. Cells with mutated PTEN had the highest IGFBP-3 expression and the slowest migration rates. This study demonstrates that endogenous IGFBP-3 modulates adhesion-migration dynamics in EC cells, implying that it may be important in regulating metastasis in this disease.
细胞迁移和侵袭导致转移是子宫内膜癌（EC）死亡的主要原因。我们已经表明，EC 细胞迁移的速度与胰岛素样生长因子结合蛋白-3（IGFBP-3）的水平呈负相关。用 siRNA 下调 IGFBP-3 可加速迁移而不影响增殖，细胞表现出更具迁移表型的特征，与细胞膜前缘的迁移相关标记物共定位。用重组 IGFBP-3 或 IGFBP-3 的过表达则会产生相反的效果。具有突变 PTEN 的细胞具有最高的 IGFBP-3 表达和最慢的迁移速度。这项研究表明，内源性 IGFBP-3 调节 EC 细胞的黏附-迁移动力学，这意味着它可能在调节这种疾病的转移中很重要。
