Inhibition of metastasis of oral squamous cell carcinoma by anti-PLGF treatment
Inhibition of metastasis of oral squamous cell carcinoma by anti-PLGF treatment
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DOI：
10.1007/s13277-014-2892-y
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发表时间：
2015-04-01
期刊：
影响因子：
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通讯作者：
Chen, Peng
中科院分区：
文献类型：
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作者：
Bu, Jingqiu;Bu, Xi;Chen, Peng
新生血管在肿瘤转移中起着关键作用。然而，调控口腔鳞状细胞癌（OSCC）新生血管形成的分子机制尚不清楚。胎盘生长因子（PLGF）已被认为是调节病理性血管生成，最近已被证明可以调节基质金属蛋白酶（MMPs）的细胞外基质降解过程中新血管形成。在此，我们的目的是研究PLGF是否可以调节MMPs在口腔鳞癌的转移。我们发现PLGF和MMP 9在口腔鳞癌患者中的水平密切相关，两者在原发性口腔鳞癌转移患者的口腔鳞癌中均升高。因此，我们使用了几种人口腔鳞癌细胞系来研究PLGF和MMP 9之间的关系。我们发现PLGF在OSCC细胞中的过表达增加了MMP 9的表达，而PLGF在OSCC细胞中的抑制降低了MMP 9的表达。然而，MMP 9在OSCC细胞中的水平的适应并不影响PLGF的水平。这些数据表明，PLGF可以调节MMP 9在口腔鳞癌细胞，但不是反之亦然。此外，抑制ERK 1/2，而不是抑制PI 3 k或JNK途径，基本上取消了PLGF对MMP 9的作用，这表明PLGF可能通过ERK/MAPK信号通路增加MMP 9的表达。因此，我们的数据表明，PLGF诱导的癌症新生血管可能部分介导的MMP 9激活在口腔鳞癌的影响。
Neovascularization plays a critical role in cancer metastasis. However, the molecular mechanism regulating the neovascularization in oral squamous cell carcinoma (OSCC) is poorly understood. Placental growth factor (PLGF) has been known to regulate pathological angiogenesis and has been recently shown to regulate matrix metalloproteinases (MMPs) for extracellular matrix degradation during neovascularization. Here we aimed to examine whether PLGF may regulate MMPs in the metastasis of OSCC. We found that PLGF and MMP9 levels strongly correlated in OSCC in the patients, both increased in the OSCC from the patients with metastasis of the primary OSCC. Thus, we used several human OSCC cell lines to examine the relationship between PLGF and MMP9. We found that overexpression of PLGF in OSCC cells increased expression of MMP9, while inhibition of PLGF in OSCC cells decreased expression of MMP9. However, adaptation of MMP9 levels in OSCC cells did not affect the levels of PLGF. These data suggest that PLGF may regulate MMP9 in OSCC cells, but not vice versa. Moreover, inhibition of ERK1/2, but not inhibition of PI3k or JNK pathways, substantially abolished the effect of PLGF on MMP9, suggesting that PLGF may increase expression of MMP9 via ERK/MAPK signaling pathway. Thus, our data demonstrate that PLGF-induced cancer neovascularization may be partially mediated through its effect on MMP9 activation in OSCC.