title: Tissue inhibitor of metalloproteinases in oral squamous cell carcinomas - a therapeutic target?
abstract: Matrix metalloproteinases (MMPs) are proteases responsible for remodeling the extracellular matrix (ECM) and enabling spreading and metastasis of tumor cells, a common phenomenon in oral squamous cell carcinomas (OSCC). They are strongly blocked by several inhibitors, among which we must highlight, for their specificity and potency, the endogenous tissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4). The goal of this paper is to describe the expression of TIMPs in OSCC, determining their relation with clinical, histological and prognostic factors, delving into OSCC regulation mechanisms and discussing the use of exogenous TIMPs to treat this type of tumors. Expression of TIMPs in OSCC is higher in tumors than in normal tissue, which correlates with an increase of metastatic risk and regional lymph node affectation. Although some metalloproteinases inhibitors (MMIs) have shown promising results in the treatment of these tumors, their use in OSCC has not been widely tested; and although some indirect MMIs, like COX-2 inhibitors, flavonoids and endostatin seem to have beneficial effects on the invasive capacity of OSCC through regulation of MMPs and TIMP levels, routine clinical use has not been accepted yet.
authors.affiliation: Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Entrerríos s/n, Santiago de Compostela C.P. 15782, Spain. Electronic address: perezsayans@gmail.com.
authors.forename: Mario
authors.initials: M
authors.lastname: Pérez-Sayáns
authors.affiliation: Servicio de Anatomia Patológica, Hospital Clinico Universitario de Santiago, Choupana s/n, Santiago de Compostela C.P. 15706, Spain. Electronic address: jm.suarez.penaranda@gmail.com.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Suárez-Peñaranda
authors.affiliation: Clinical Epidemiology and Biostatistics Unit, Hospital Clínico Universitario de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), A Choupana s/n, Santiago de Compostela 15706, Spain. Electronic address: pilar.gayoso.diz@sergas.es.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gayoso-Diz
authors.affiliation: Unidad de Medicina Molecular, Fundación Pública Galega de Medicina Xenómica, Edificio de Consultas planta-2, Hospital Clinico Universitario, Santiago de Compostela C.P. 15706, Spain. Electronic address: francisco.barros@usc.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Barros-Angueira
authors.affiliation: Entrerríos s/n, Santiago de Compostela C.P. 15782, Spain. Electronic address: josemanuel.gandara@usc.es.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Gándara-Rey
authors.affiliation: Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Entrerríos s/n, Santiago de Compostela C.P. 15782, Spain. Electronic address: abel.garcia@usc.es.
authors.forename: Abel
authors.initials: A
authors.lastname: García-García
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases