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 language | English |
|---|---|
| Pages (from-to) | 332-338 |
| Number of pages | 7 |
| Journal | Lung Cancer |
| Volume | 76 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jun 2012 |
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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 journal › Article
}
TY - JOUR
T1 - Soluble epidermal growth factor receptor isoforms in non-small cell lung cancer tissue and in blood
AU - Maramotti, Sally
AU - Paci, Massimiliano
AU - Miccichè, Francesca
AU - Ciarrocchi, Alessia
AU - Cavazza, Alberto
AU - De Bortoli, Maida
AU - Vaghi, Elena
AU - Formisano, Debora
AU - Canovi, Laura
AU - Sgarbi, Giorgio
AU - Bongarzone, Italia
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Isoforms, Isoelectric point
KW - Non-small cell lung cancer
KW - Shedding, OFFGEL electrophoresis
KW - Soluble epidermal growth factor receptor
UR - http://www.scopus.com/inward/record.url?scp=84860507315&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860507315&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2011.11.018
DO - 10.1016/j.lungcan.2011.11.018
M3 - Article
C2 - 22177532
AN - SCOPUS:84860507315
VL - 76
SP - 332
EP - 338
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
IS - 3
ER -