Institute of Carcinogenesis, Blokhin Russian Cancer Research Center, Moscow, Russia.
Oncogene. 2012 Mar 15;31(11):1389-97. doi: 10.1038/onc.2011.330. Epub 2011 Aug 1.
Experimental and clinical studies positively correlate expression of vascular endothelial growth factor (VEGF)-C in cancer cells with accelerated tumor progression and/or unfavorable clinical outcome. However, many aspects of tumor-promoting activity of VEGF-C and consequences of its downregulation for tumor progression remain poorly understood. To clarify these points, we created a set of VEGF receptor 3-positive lung carcinoma A549 and colon carcinoma HCT116 cell sublines with stable repression of VEGF-C synthesis. Analysis of the behavior of these cells revealed multiple effects of VEGF-C downregulation, which, in addition to deceleration of cell proliferation and invasion in vitro and inhibition of lymphangiogenesis in tumor and surrounding tissues observed earlier, included previously undescribed effects, in particular, partial restoration of epithelial phenotype, reduction in the percentage of tumor-initiating cells (cancer stem cells) in the cell population and inhibition of metastasis of orthotopic lung cancer xenografts to other lung lobes. These results are consistent with the idea of high potentiality of VEGF-C as a cancer drug target.
实验和临床研究表明，癌细胞中血管内皮生长因子 C (VEGF-C) 的表达与肿瘤的加速进展和/或不良临床结局呈正相关。然而，VEGF-C 的促肿瘤活性的许多方面及其对肿瘤进展的下调后果仍知之甚少。为了阐明这些问题，我们构建了一组 VEGF 受体 3 阳性肺腺癌 A549 和结肠癌细胞 HCT116 的细胞亚系，其 VEGF-C 的合成被稳定抑制。对这些细胞行为的分析揭示了 VEGF-C 下调的多种作用，除了先前观察到的体外细胞增殖和侵袭的减缓以及肿瘤和周围组织中淋巴管生成的抑制之外，还包括以前未描述的作用，特别是上皮表型的部分恢复、肿瘤起始细胞（癌症干细胞）在细胞群体中的比例降低以及对原位肺癌异种移植物向其他肺叶转移的抑制。这些结果与 VEGF-C 作为癌症药物靶点的高潜力的观点一致。
