title: Metalloproteinases ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas.
abstract: Invasion of tumor cells critically depends on cell-cell or cell-extracellular matrix interactions. Enzymes capable of modulating these interactions belong to the proteinase families of ADAM (a disintegrin and metalloprotease) and MMP (matrix metalloprotease) proteins. Our objective is to examine their expression levels and evaluate the relationship between expression levels and cavernous sinus invasion in pituitary adenomas. Tissue samples from 35 patients with pituitary adenomas were analyzed. Quantitative real-time polymerase chain reaction (qPCR) was employed to assess mRNA expression levels for ADAM and MMP genes. Protein levels were examined using immunohistochemistry and Western Blot. Correlation analyses between expression levels and clinical parameters were performed. By silencing ADAM12 and MMP-14 with siRNA in a mouse pituitary adenoma cell line (TtT/GF), their cellular effects were investigated. In our study, nine women and 26 men were included, with a mean age of 53.1 years (range 15-84 years) at the time of surgery. There were 19 cases with cavernous sinus invasion. The proteins ADAM12 and MMP-14 were significantly up-regulated in invasive adenomas compared to noninvasive adenomas. Both human isoforms of ADAM12 (ADAM12L and ADAM12s) were involved in tumor invasion; moreover, ADAM12L was found to correlate positively with Ki-67 proliferation index in pituitary adenomas. In TtT/GF pituitary adenoma cells, silencing of ADAM12 and MMP-14 significantly inhibited cell invasion and migration, respectively, whereas only silencing of ADAM12 suppressed cell proliferation. We conclude that ADAM12 and MMP-14 are associated with cavernous sinus invasion in pituitary adenomas, which qualifies these proteins in diagnosis and therapy.
authors.affiliation: Department of Neurosurgery, University Marburg, Baldingerstrasse, Marburg, 35033, Germany.|Department of Neurosurgery, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, University Marburg, Baldingerstrasse, Marburg, 35033, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Voellger
authors.affiliation: Department of Neurosurgery, University Marburg, Baldingerstrasse, Marburg, 35033, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Benzel
authors.affiliation: Department of Neurosurgery, University Marburg, Baldingerstrasse, Marburg, 35033, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlomann
authors.affiliation: Department of Neurosurgery, University Marburg, Baldingerstrasse, Marburg, 35033, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Nimsky
authors.affiliation: Department of Neurosurgery, University Marburg, Baldingerstrasse, Marburg, 35033, Germany.
authors.forename: Jörg W
authors.initials: JW
authors.lastname: Bartsch
authors.affiliation: Department of Neurosurgery, University Marburg, Baldingerstrasse, Marburg, 35033, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Carl
mesh_terms: D000072199:ADAM12 Protein / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers; D002426:Cavernous Sinus / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D053511:Matrix Metalloproteinase 14
keywords: ADAM12; MMP-14; cavernous sinus invasion; pituitary adenomas