Laboratory for Molecular Cellular Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna 1090, Austria.
Int J Mol Sci. 2013 Sep 3;14(9):17958-71. doi: 10.3390/ijms140917958.
The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF). PlGF is a member of the vascular endothelial growth factor (VEGF) family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.
前列腺癌的生长和血管生成依赖于癌细胞与支持性基质细胞之间的相互作用。在前列腺肿瘤中发现的主要基质细胞类型是癌相关成纤维细胞，其产生胎盘生长因子（PlGF）。PlGF 是血管内皮生长因子（VEGF）家族中一种血管生成分子，在前列腺癌去势治疗后 PlGF mRNA 水平增加。在这项研究中，我们表明 PlGF 在体外对人 PC-3 前列腺癌细胞具有直接的剂量依赖性增殖作用，成纤维细胞衍生的 PlGF 在共培养中增加了 PC-3 的增殖。在异种移植肿瘤模型中，肿瘤内给予鼠 PlGF siRNA 可降低基质衍生的 PlGF 表达，减少肿瘤负担，并减少与血管密度降低相关的 Ki-67 阳性增殖细胞的数量。这些数据表明，靶向基质 PlGF 表达可能是治疗前列腺癌的一种治疗靶点。
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