title: Soluble epidermal growth factor receptor isoforms in non-small cell lung cancer tissue and in blood.
abstract: Epidermal growth factor receptor (EGFR) is implicated in tumor development and is highly expressed in many human tumors. EGFR overexpression has been observed in both premalignant lesions and in malignant lung tumors, as well as in 40-80% of patients with non-small cell lung cancer (NSCLC). EGFR is a 170-kDa transmembrane glycoprotein with an extracellular ligand-binding domain and a cytoplasmic domain with intrinsic tyrosine kinase activity. Soluble forms of EGFR (sEGFR) containing the extracellular domain have been described both in conditioned media from EGFR overexpressing cells as well as in peripheral blood. However, very little is known regarding the molecular function and the biochemical properties of these circulating EGFR isoforms. This study investigates the expression of sEGFR in lung cancer cultured cells and NSCLC patients with the aim of identifying clinically relevant isoforms specifically produced by tumor cells. Proteomic approaches including OFFGEL electrophoresis and Western blotting analysis were used to assess the sEGFR expression pattern in primary lung tumor samples, normal counterparts and matched plasma. We discover that the isoelectric points of sEGFR isoforms in NSCLC biopsy tissue differ from those of the isoforms present in healthy tissue and detected in the plasma of all subjects. These results demonstrate, for the first time, the existence of sEGFR isoforms specifically produced by NSCLC tumor cells which could represent a new potential biomarker for diagnosis and therapy of lung tumors. However, our observations indicate that more highly sensitive and specific quantitative assays are needed in order to reliably detect the tumor-associated sEGFR isoforms in plasma samples.
authors.affiliation: Molecular Biology Laboratory, Department of Oncology, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy. sally.maramotti@asmn.re.it
authors.forename: Sally
authors.initials: S
authors.lastname: Maramotti
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Paci
authors.forename: Francesca
authors.initials: F
authors.lastname: Miccichè
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciarrocchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Cavazza
authors.forename: Maida
authors.initials: M
authors.lastname: De Bortoli
authors.forename: Elena
authors.initials: E
authors.lastname: Vaghi
authors.forename: Debora
authors.initials: D
authors.lastname: Formisano
authors.forename: Laura
authors.initials: L
authors.lastname: Canovi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sgarbi
authors.forename: Italia
authors.initials: I
authors.lastname: Bongarzone
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000378:metabolism*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000737:chemistry; D066246:ErbB Receptors / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism*; D020033:Protein Isoforms / Q000097:blood / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D020033:Protein Isoforms; D066246:ErbB Receptors