Bachelder Robin E, Wendt Melissa A, Mercurio Arthur M
Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Cancer Res. 2002 Dec 15;62(24):7203-6.
We report that vascular endothelial growth factor (VEGF), a major angiogenic factor, is also arequisite autocrine factor for breast carcinoma invasion in vitro and that the VEGF receptor Neuropilin-1 but not Flt-1 is essential for this function. VEGF regulates expression of the chemokine receptor CXCR4, and this VEGF target is needed for invasion but not for cell survival. CXCR4 mediates migration of breast carcinoma cells toward stromal-derived factor-1, and this migration is dependent on autocrine VEGF. Of interest, a CXCR4-inhibitory peptide that is currently in HIV clinical trials suppressed invasion. Our findings indicate that a VEGF autocrine pathway induces chemokine receptor expression in breast carcinoma cells, thus promoting their directed migration toward specific chemokines.
我们报告称，血管内皮生长因子（VEGF）作为一种主要的血管生成因子，也是体外乳腺癌侵袭所必需的自分泌因子，且VEGF受体神经纤毛蛋白-1（Neuropilin-1）而非Flt-1对该功能至关重要。VEGF调节趋化因子受体CXCR4的表达，且该VEGF靶点是侵袭所必需的，但对细胞存活并非必需。CXCR4介导乳腺癌细胞向基质衍生因子-1的迁移，且这种迁移依赖于自分泌的VEGF。有趣的是，一种目前正在进行HIV临床试验的CXCR4抑制肽可抑制侵袭。我们的研究结果表明，VEGF自分泌途径可诱导乳腺癌细胞趋化因子受体表达，从而促进其向特定趋化因子的定向迁移。
