Development of biological tools to assess the role of TMPRSS4 and identification of novel tumor types with high expression of this prometastatic protein
Maria Villalba1,2, Lissett Lopez3, Miriam Redrado1, Tamara Ruiz3, Arrate L. de Aberasturi1,2, Nuria de la Roja3, David Garcia2, Francisco Exposito1,2, Carlos de Andrea2, Emilio Alvarez-Fernandez4, Luis Montuenga1,2, Paloma Rueda3, Maria Jose Rodriguez3 and Alfonso Calvo1,2
1IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), Pamplona, Spain, 2Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Spain, 3Inmunología y Genética Aplicada, S.A. (Ingenasa) and 4Department of Pathology, Gregorio Marañon Hospital, Madrid, Spain
Offprint requests to: Alfonso Calvo, Laboratory 2.03, Solid Tumors and Biomarkers Program, Center for Applied Medical Research (CIMA), Avenida Pio XII, 55, 31008 Pamplona, Spain. e-mail: acalvo@unav.es
Summary. 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, in which TMPRSS4 expression 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-TMPRSS4 drugs. Future studies should determine the clinical value of assessing TMPRSS4 levels in different types of lung cancer. Histol Histopathol 32, 929-940 (2017)
Key words: TMPRSS4, Recombinant proteins, Cancer biomarkers, Squamous lung carcinomas
DOI: 10.14670/HH-11-857