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

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

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Received: 6 June 2011; in revised form: 13 June 2011 / Accepted: 15 June 2011 / Published: 23 June 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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.
Abstract: 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  
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MDPI and ACS Style

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.

AMA Style

Xiao Z, Liu Q, Mao F, Wu J, Lei T. TNF-α-Induced VEGF and MMP-9 Expression Promotes Hemorrhagic Transformation in Pituitary Adenomas. International Journal of Molecular Sciences. 2011; 12(6):4165-4179.

Chicago/Turabian Style

Xiao, Zhengzheng; Liu, Qin; Mao, Feng; Wu, Jun; Lei, Ting. 2011. "TNF-α-Induced VEGF and MMP-9 Expression Promotes Hemorrhagic Transformation in Pituitary Adenomas." Int. J. Mol. Sci. 12, no. 6: 4165-4179.

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