title: Development of biological tools to assess the role of TMPRSS4 and identification of novel tumor types with high expression of this prometastatic protein.
abstract: Metastatic spread is responsible for the majority of cancer deaths and identification of metastasis-related therapeutic targets is compulsory. TMPRSS4 is a pro-metastatic druggable transmembrane type II serine protease whose expression has been associated with the development of several cancer types and poor prognosis. To study the role and expression of this protease in cancer, we have developed molecular tools (active recombinant proteins and a polyclonal antibody) that can be used for diagnostic purposes and for testing anti-TMPRSS4 drugs. In addition, we have evaluated TMPRSS4 protein expression in several cancer tissue microarrays (TMAs). Full length and truncated TMPRSS4 recombinant proteins maintained the catalytic activity in two different expression systems (baculovirus and E. coli). Sensitivity of the rabbit polyclonal antisera against TMPRSS4 (ING-pAb) outperformed the antibody most commonly used in clinical settings. Analysis by immunohistochemistry in the different TMAs identified a subset of adenocarcinomas, squamous carcinomas, large cell carcinomas and carcinoids of the lung, which may define aggressive tumors. In conclusion, our biological tools will help the characterization of TMPRSS4 activity and protein expression, as well as the evaluation of anti-TMRSS4 drugs. Future studies should determine the clinical value of assessing TMPRSS4 levels in different types of lung cancer.
authors.affiliation: IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain.|Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Villalba
authors.affiliation: Inmunología y Genética Aplicada, S.A. (Ingenasa), Madrid, Spain.
authors.forename: Lissett
authors.initials: L
authors.lastname: Lopez
authors.affiliation: IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Redrado
authors.affiliation: Inmunología y Genética Aplicada, S.A. (Ingenasa), Madrid, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Ruiz
authors.affiliation: IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain.|Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Arrate L
authors.initials: AL
authors.lastname: de Aberasturi
authors.affiliation: Inmunología y Genética Aplicada, S.A. (Ingenasa), Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: de la Roja
authors.affiliation: Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Garcia
authors.affiliation: IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain.|Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Exposito
authors.affiliation: Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: de Andrea
authors.affiliation: Department of Pathology, Gregorio Marañon Hospital, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Alvarez-Fernandez
authors.affiliation: IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain.|Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Montuenga
authors.affiliation: Inmunología y Genética Aplicada, S.A. (Ingenasa), Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Rueda
authors.affiliation: Inmunología y Genética Aplicada, S.A. (Ingenasa), Madrid, Spain.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Rodriguez
authors.affiliation: IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain. acalvo@unav.es.|Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Calvo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D004926:Escherichia coli; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D008565:Membrane Proteins; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; C528837:TMPRSS4 protein, human