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Int. J. Mol. Sci. 2011, 12(6), 4165-4179; doi:10.3390/ijms12064165

TNF-α-Induced VEGF and MMP-9 Expression Promotes Hemorrhagic Transformation in Pituitary Adenomas

Received: 6 June 2011 / Revised: 13 June 2011 / Accepted: 15 June 2011 / Published: 23 June 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Pituitary apoplexy is a clinical syndrome with unknown pathogenesis. Therefore, identifying the underlying mechanisms is of high clinical relevance. Tumor necrosis factor alpha (TNF-α) is a critical cytokine mediating various hemorrhagic events, but little is known about its involvement in pituitary apoplexy. Here we show that TNF-α may be an important regulator of hemorrhagic transformation in pituitary adenomas. In this study, sixty surgical specimens of hemorrhagic and non-hemorrhagic human pituitary adenomas were examined. Hemorrhagic pituitary adenomas displayed higher protein and mRNA levels of TNF-α, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) compared with those of non-hemorrhagic tumors. Exposure of MMQ pituitary adenoma cells to TNF-α induced VEGF and MMP-9 expression in vitro. Additionally, TNF-α administration caused hemorrhagic transformation and enhanced VEGF and MMP-9 expression in MMQ pituitary adenoma cell xenografts in mice. Blockers of VEGF or MMP-9, either alone or in combination, attenuated but not abrogated TNF-α mediated hemorrhagic transformation in xenografts. This study suggests that TNF-α may play a role in the development of intratumoral hemorrhage in pituitary adenomas via up-regulation of VEGF and MMP-9.
Keywords: pituitary apoplexy; intratumoral hemorrhage; TNF-α; VEGF; MMP-9   pituitary apoplexy; intratumoral hemorrhage; TNF-α; VEGF; MMP-9  
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Xiao, Z.; Liu, Q.; Mao, F.; Wu, J.; Lei, T. TNF-α-Induced VEGF and MMP-9 Expression Promotes Hemorrhagic Transformation in Pituitary Adenomas. Int. J. Mol. Sci. 2011, 12, 4165-4179.

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