title: Expression of MMP14 in invasive pituitary adenomas: relationship to invasion and angiogenesis.
abstract: Pituitary adenomas (PAs) are noncancerous tumors, and about 35% of those reported to be invasive have been classified as "invasive pituitary adenomas (IPAs)". In clinical, operative complications, total resection failures, and high relapse rates result from invasive features during the therapeutic process. Invasive mechanism is a complex process, including metalloproteases, inhibitors and tumor microenvironment factors etc. Thus, studying invasive mechanism of PAs might contribute to understanding its biological behavior. In our research, three type tissue samples of human, pituitaries, PAs, IPAs, their mRNA expression of MMP1, MMP2, MMP9, MMP14 and MMP15 were measured using real-time PCR. MMP2 and MMP14 protein levels also were measured with immunohistochemistry in same samples. We confirmed that elevated matrix metalloproteinase-14 expression correlates with invasive characteristics of IPAs. To investigate molecular mechanism of how MMP14 contributes to invasiveness, an ATT20 cell was used in this study. After transient-transfection of the MMP14-shRNA expression vector into ATT20 cells, we observed that mRNA expression of PTTG, VEGF, and TGFβ was significantly suppressed in interference groups. Meanwhile, ATT20 cells in high concentration TIMP-1 environment exhibit reduced PTTG, VEGF, and TGFβ expression accompanied with the down-regulation of MMP14. Thus, we propose that MMP14 plays an important role in tumor invasion and angiogenesis and that a novel regulatory pathway for MMP14 may exist through VEGF and PTTG. In brief, MMP14 may be a target for therapeutic treatment.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University Suzhou 215006, China ; Department of Neurosurgery, The First Affiliated Hospital of Soochow University Suzhou 215004, China.
authors.forename: Pinjing
authors.initials: P
authors.lastname: Hui
authors.affiliation: Department of Biochemical and Molecular Biology Medical College, Soochow University Suzhou 215123, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biochemical and Molecular Biology Medical College, Soochow University Suzhou 215123, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Soochow University Suzhou 215004, China.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Hui
authors.affiliation: Department of Biochemical and Molecular Biology Medical College, Soochow University Suzhou 215123, China.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University Suzhou 215006, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D064249:Securin / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D064249:Securin; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C578002:pituitary tumor-transforming protein 1, human; D020782:Matrix Metalloproteinases; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: ATT20; MMP14; PTTG; VEGF; invasive pituitary adenomas