Thyroid carcinoma cells produce PLGF to enhance metastasis.

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.