Fan Fan, Wey Jane S, McCarty Marya F, Belcheva Anna, Liu Wenbiao, Bauer Todd W, Somcio Ray J, Wu Yan, Hooper Andrea, Hicklin Daniel J, Ellis Lee M
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Oncogene. 2005 Apr 14;24(16):2647-53. doi: 10.1038/sj.onc.1208246.
Vascular endothelial growth factor (VEGF) is associated with tumor angiogenesis and poor prognosis in human colorectal cancer (CRC). VEGF receptor-1 (VEGFR-1 or Flt-1) is a high-affinity receptor for VEGF and is typically considered specific to endothelial cells. Here we report the expression and function of VEGFR-1 in CRC cell lines. VEGFR-1 was expressed in all CRC cell lines studied as determined by RT-PCR, Western blot analysis, FACS, and ELISA. Treatment of the human CRC cell lines HT-29 and SW480 with VEGF-A (a ligand for both VEGFR-1 and -2) or VEGF-B (a ligand specific for VEGFR-1) led to activation of Erk-1/2, SAPK/JNK, and translocation of the p65 subunit of nuclear factor-kappaB into the nucleus. Both VEGF-A and -B led to significant induction of cell motility and invasiveness of CRC cells. Stimulation of cells with VEGF-A or -B also led to larger and more numerous colonies in soft agar. However, activation of VEGFR-1 did not increase CRC cell proliferation. In contrast to the previous paradigm that VEGFRs are not present on tumor cells of epithelial origin, we found that VEGFR-1 is present and functional on CRC cells, and activation by VEGF family ligands can activate processes involved in tumor progression and metastasis.
血管内皮生长因子（VEGF）与人类结直肠癌（CRC）的肿瘤血管生成及不良预后相关。VEGF受体-1（VEGFR-1或Flt-1）是VEGF的高亲和力受体，通常被认为是内皮细胞特有的。在此，我们报告VEGFR-1在结直肠癌细胞系中的表达及功能。通过逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹分析、荧光激活细胞分选术（FACS）及酶联免疫吸附测定（ELISA）确定，VEGFR-1在所研究的所有结直肠癌细胞系中均有表达。用VEGF-A（VEGFR-1和-2的配体）或VEGF-B（VEGFR-1特异性配体）处理人结直肠癌细胞系HT-29和SW480，可导致细胞外信号调节激酶-1/2（Erk-1/2）、应激激活蛋白激酶/应激活化蛋白激酶（SAPK/JNK）激活，以及核因子κB（NF-κB）的p65亚基转位至细胞核。VEGF-A和-B均能显著诱导结直肠癌细胞的细胞运动性及侵袭性。用VEGF-A或-B刺激细胞还可导致软琼脂中形成更大且更多的集落。然而，VEGFR-1的激活并未增加结直肠癌细胞的增殖。与之前认为VEGFRs不存在于上皮源性肿瘤细胞上的范例相反，我们发现VEGFR-1存在于结直肠癌细胞上且具有功能，VEGF家族配体的激活可激活参与肿瘤进展和转移的过程。
