title: Characterization of matrix metalloproteinase-2 and -9, ADAM-10 and N-cadherin expression in human glioblastoma multiforme.
abstract: Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in humans, whose invasiveness and proliferation are associated with poor prognosis. Matrix metalloproteinases (MMPs) and the related family of "a disintegrin and metalloproteinase" (ADAM) both contribute to increase cell invasion, and its substrate N-cadherin is involved in proliferation and metastatic capacities of tumor cells. However, these molecular determinants of aggressiveness have not been adequately characterized in GBM. In an attempt to better define these pathogenetic signatures, in the present study we evaluated the comparative expression of two main MMPs (MMP-2 and -9), as well as of ADAM-10 and N-cadherin in surgical samples from patients diagnosed with WHO grade IV GBM (n = 25) and in cortical tissue specimens obtained from untreatable epileptic patients (controls, n = 8) through a series of histopathological, immunohistochemical and biochemical tests. Our studies revealed that both MMP-2 and -9 immunoreactivities (IRs) were upregulated in 13 of 25 (52 %) and 19 of 25 (76 %) GBMs, respectively, and the extent of the increase was highly significant with respect to controls (p < 0.001). ADAM-10 IR was also found to be increased (p < 0.001) in 16 of 25 GBM specimens (64 %). Conversely, N-cadherin IR was remarkably decreased (p < 0.001) in almost the totality of tumor samples (22 of 25, 88 %). A similar trend was also obtained at the mRNA and protein level by qPCR and western blot analyses, respectively. Collectively, the current study provides a comprehensive molecular portrayal of some of the major pathological hallmarks of GBM aggressiveness, which could be exploitable as potential targets for a new therapeutic approach.
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Human Anatomy and Histology, School of Medicine, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumeci
authors.affiliation: Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele", Section of Anatomic Pathology, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Magro
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Physiology, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.
authors.forename: Venera
authors.initials: V
authors.lastname: Cardile
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Physiology, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Coco
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Human Anatomy and Histology, School of Medicine, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.
authors.forename: Rubina
authors.initials: R
authors.lastname: Marzagalli
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Human Anatomy and Histology, School of Medicine, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Castrogiovanni
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Human Anatomy and Histology, School of Medicine, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Imbesi
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Physiology, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.
authors.forename: Adriana Carol Eleonora
authors.initials: AC
authors.lastname: Graziano
authors.affiliation: Neurosurgery Unit, Cannizzaro Hospital, Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Barone
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Pathology, School of Medicine, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.
authors.forename: Michelino
authors.initials: M
authors.lastname: Di Rosa
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Human Anatomy and Histology, School of Medicine, University of Catania, Via S. Sofia 87, 95125, Catania, Italy.|Neurosurgery Unit, Fondazione Mediterranea "G.B. Morgagni", Catania, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Castorina
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Section of Human Anatomy and Histology, School of Medicine, University of Catania, Via S. Sofia 87, 95125, Catania, Italy. alecasto@unict.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Castorina
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000096:biosynthesis* / Q000235:genetics; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C050361:CDH2 protein, human; D015820:Cadherins; D008565:Membrane Proteins; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: ADAM-10; Glial tumors; Glioblastoma multiforme; Matrix metalloproteinase; N-cadherin