He Junyi, Shen Na, Huang Xinsheng
Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Department of Otolaryngology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Tumour Biol. 2015 Nov;36(11):8601-7. doi: 10.1007/s13277-015-3548-2. Epub 2015 Jun 4.
Cancer neovascularization is essential for metastasis of thyroid carcinoma. However, the underlying molecular mechanisms are ill-defined. Recently, placental growth factor (PLGF) has been shown to play critical roles in the pathological angiogenesis through regulating matrix metalloproteinases (MMPs); here, we were prompted to examine the role of PLGF in the metastasis of thyroid carcinoma. We found that the PLGF and MMP9 levels strongly correlated in the thyroid carcinoma specimen. Higher PLGF and MMP9 levels were detected in the thyroid carcinoma with metastasis. Using a human thyroid carcinoma cell line, TT, we found that overexpression of PLGF in TT cells increased expression of MMP9, while inhibition of PLGF in TT cells decreased expression of MMP9. However, modification of MMP9 levels in TT cells did not affect PLGF levels, suggesting that PLGF may regulate MMP9 in thyroid carcinoma cells. Moreover, application of a specific MAPK p42/p44 inhibitor, but not the application of a specific MAPK p38 inhibitor or specific Akt or JNK inhibitors, substantially abolished the effect of PLGF on MMP9 activation, suggesting that PLGF may increase expression of MMP9 via p42/p44 signaling pathway. Together, these data suggest that antagonizing PLGF in thyroid carcinoma cells may be a promising therapy to suppress cancer metastasis.
肿瘤新生血管形成对于甲状腺癌转移至关重要。然而，其潜在的分子机制尚不明确。最近，胎盘生长因子（PLGF）已被证明通过调节基质金属蛋白酶（MMPs）在病理性血管生成中发挥关键作用；在此，我们着手研究PLGF在甲状腺癌转移中的作用。我们发现，在甲状腺癌标本中PLGF和MMP9水平密切相关。在发生转移的甲状腺癌中检测到更高的PLGF和MMP9水平。使用人甲状腺癌细胞系TT，我们发现TT细胞中PLGF的过表达增加了MMP9的表达，而TT细胞中PLGF的抑制降低了MMP9的表达。然而，TT细胞中MMP9水平的改变并不影响PLGF水平，这表明PLGF可能在甲状腺癌细胞中调节MMP9。此外，应用特异性MAPK p42/p44抑制剂，但不应用特异性MAPK p38抑制剂或特异性Akt或JNK抑制剂，可显著消除PLGF对MMP9激活的作用，这表明PLGF可能通过p42/p44信号通路增加MMP9的表达。总之，这些数据表明，拮抗甲状腺癌细胞中的PLGF可能是一种有前景的抑制癌症转移的治疗方法。
