Soluble epidermal growth factor receptor isoforms in non-small cell lung cancer tissue and in blood

Sally Maramotti, Massimiliano Paci, Francesca Miccichè, Alessia Ciarrocchi, Alberto Cavazza, Maida De Bortoli, Elena Vaghi, Debora Formisano, Laura Canovi, Giorgio Sgarbi, Italia Bongarzone

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)332-338
Number of pages7
JournalLung Cancer
Volume76
Issue number3
DOIs
Publication statusPublished - Jun 2012

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein Isoforms
Neoplasms
Lung
Isoelectric Point
Conditioned Culture Medium
Proteomics
Protein-Tyrosine Kinases
Electrophoresis
Cultured Cells
Lung Neoplasms
Glycoproteins
Biomarkers
Western Blotting
Ligands
Biopsy

Keywords

  • Isoforms, Isoelectric point
  • Non-small cell lung cancer
  • Shedding, OFFGEL electrophoresis
  • Soluble epidermal growth factor receptor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Soluble epidermal growth factor receptor isoforms in non-small cell lung cancer tissue and in blood. / Maramotti, Sally; Paci, Massimiliano; Miccichè, Francesca; Ciarrocchi, Alessia; Cavazza, Alberto; De Bortoli, Maida; Vaghi, Elena; Formisano, Debora; Canovi, Laura; Sgarbi, Giorgio; Bongarzone, Italia.

In: Lung Cancer, Vol. 76, No. 3, 06.2012, p. 332-338.

Research output: Contribution to journalArticle

Maramotti, Sally ; Paci, Massimiliano ; Miccichè, Francesca ; Ciarrocchi, Alessia ; Cavazza, Alberto ; De Bortoli, Maida ; Vaghi, Elena ; Formisano, Debora ; Canovi, Laura ; Sgarbi, Giorgio ; Bongarzone, Italia. / Soluble epidermal growth factor receptor isoforms in non-small cell lung cancer tissue and in blood. In: Lung Cancer. 2012 ; Vol. 76, No. 3. pp. 332-338.
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