Molecular Network Basis of Invasive Pituitary Adenoma: A Review

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.

Keywords: angiogenesis; endocrinology; invasiveness; molecular network; pituitary adenoma.

Figure 1

VEGF secreted by tumor cells promotes neovascularization via downstream pathways including the MAPK signaling pathway, FAK pathway, PI3K/Akt pathway, and p38 MAP kinase pathway, it also directly promotes tumor cell proliferation. IP3 pathway and VEGF-induced immune escape might be involved in invasiveness of the pituitary adenoma.

Figure 2

Interaction of core molecules with each other and their relationship with EMT, angiogenesis, and ECM degradation. 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.