Abstract
Cases with pituitary adenoma comprise 10–25% of intracranial neoplasm, being the third most common intracranial tumor, most of the adenomas are considered to be benign. About 35% of pituitary adenomas are invasive. This review summarized the known molecular basis of the invasiveness of pituitary adenomas. The study pointed out that hypoxia-inducible factor-1α, pituitary tumor transforming gene, vascular endothelial growth factor, fibroblast growth factor-2, and matrix metalloproteinases (MMPs, mainly MMP-2, and MMP-9) are core molecules responsible for the invasiveness of pituitary adenomas. The reason is that these molecules have the ability to directly or indirectly induce cell proliferation, epithelial-to-mesenchymal transition, angiogenesis, degradation, and remodeling of extracellular matrix. HIF-1α induced by hypoxia or apoplexy inside the adenoma might be the initiating factor of invasive transformation, followed with angiogenesis for overexpressed VEGF, EMT for overexpressed PTTG, degradation of ECM for overexpressed MMPs, creating a suitable microenvironment within the tumor. Together, they form a complex interactive network. More investigations are required to further elucidate the mechanisms underlying the invasiveness of pituitary adenomas.
Highlights
Cases with pituitary adenoma comprise 10–25% of intracranial neoplasm [1] and has a prevalence rate of about 17% in the general population [2]
This review summarized the known molecular basis of the invasiveness of invasive pituitary adenomas, providing insights for further exploration in this field
Microscopic observation of the pituitary tumor showed progressive neovascularization and remodeling of the extracellular matrix (ECM) [57]. All these findings elucidated that pituitary tumor transforming gene (PTTG), FGF-2, and Vascular endothelial growth factor (VEGF) might act in synergy from the early development to increase the invasiveness and angiogenesis of pituitary adenomas, especially prolactinoma [58] and growth hormone–secreting adenomas [59]
Summary
This review summarized the known molecular basis of the invasiveness of pituitary adenomas. The study pointed out that hypoxia-inducible factor-1α, pituitary tumor transforming gene, vascular endothelial growth factor, fibroblast growth factor-2, and matrix metalloproteinases (MMPs, mainly MMP-2, and MMP-9) are core molecules responsible for the invasiveness of pituitary adenomas. HIF-1α induced by hypoxia or apoplexy inside the adenoma might be the initiating factor of invasive transformation, followed with angiogenesis for overexpressed VEGF, EMT for overexpressed PTTG, degradation of ECM for overexpressed MMPs, creating a suitable microenvironment within the tumor. Together, they form a complex interactive network.
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