Platelet-derived growth factor-D overexpression contributes to epithelial-mesenchymal transition of PC3 prostate cancer cells
Platelet-derived growth factor-D overexpression contributes to epithelial-mesenchymal transition of PC3 prostate cancer cells
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DOI：
10.1634/stemcells.2007-1076
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发表时间：
2008-06-01
期刊：
影响因子：
5.2
通讯作者：
Sarkar, Fazlul H.
中科院分区：
文献类型：
--
作者：
Kong, Dejuan;Wang, Zhiwei;Sarkar, Fazlul H.
大多数人类恶性肿瘤被认为具有上皮起源，并且癌症的进展通常与称为上皮-间质转化（EMT）的短暂过程相关。EMT的特征在于上皮标志物的丢失和间充质标志物的获得，这是“癌症干细胞样细胞“的典型特征，其导致体内细胞侵袭和转移增加。因此，重要的是要揭示可能诱导EMT的因素在癌症进展中的机制作用。研究表明，血小板衍生生长因子（PDGF）信号有助于EMT，最近，PDGF-D已被证明可调节癌细胞侵袭和血管生成。然而，PDGF-D促进侵袭和转移的机制以及是否是由于获得EMT表型仍然是难以捉摸的。在这项研究中，我们建立了稳定转染的PC 3细胞表达高水平的PDGF-D，这导致EMT的显着诱导所示的细胞形态的变化，伴随着E-钙粘蛋白和闭锁小带-1的损失和波形蛋白的增益。我们还发现在PDGF-D PC 3细胞中，雷帕霉素和核因子-κ B的哺乳动物靶点的激活以及Bcl-2的过表达，这与增强的粘附和侵袭行为相关。更重要的是，PDGF-D过表达的PC 3细胞在SCID小鼠中的肿瘤生长速度比PC 3细胞快得多。这些结果提供了一种新的机制，PDGF-D通过这种机制促进EMT，从而增加肿瘤生长，这些结果进一步表明PDGF-D可能是预防和/或治疗前列腺癌的新的治疗靶点。
The majority of human malignancies are believed to have epithelial origin, and the progression of cancer is often associated with a transient process named epithelial-mesenchymal transition (EMT). EMT is characterized by the loss of epithelial markers and the gain of mesenchymal markers that are typical of "cancer stem-like cells, " which results in increased cell invasion and metastasis in vivo. Therefore, it is important to uncover the mechanistic role of factors that may induce EMT in cancer progression. Studies have shown that platelet-derived growth factor (PDGF) signaling contributes to EMT, and more recently, PDGF-D has been shown to regulate cancer cell invasion and angiogenesis. However, the mechanism by which PDGF-D promotes invasion and metastases and whether it is due to the acquisition of EMT phenotype remain elusive. For this study, we established stably transfected PC3 cells expressing high levels of PDGF-D, which resulted in the significant induction of EMT as shown by changes in cellular morphology concomitant with the loss of E-cadherin and zonula occludens-1 and gain of vimentin. We also found activation of mammalian target of rapamycin and nuclear factor-kappa B, as well as Bcl-2 overexpression, in PDGF-D PC3 cells, which was associated with enhanced adhesive and invasive behaviors. More importantly, PDGF-D-overexpressing PC3 cells showed tumor growth in SCID mice much more rapidly than PC3 cells. These results provided a novel mechanism by which PDGF-D promotes EMT, which in turn increases tumor growth, and these results further suggest that PDGF-D could be a novel therapeutic target for the prevention and/or treatment of prostate cancer.