Autocrine expression of the epidermal growth factor receptor ligand heparin-binding EGF-like growth factor in cervical cancer
| Autor: | Gert Jan Fleuren, Frans A. Prins, Ekaterina S. Jordanova, Arko Gorter, Michelle Osse, J. Baptist Trimbos, Marlies Schrevel |
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| Přispěvatelé: | Obstetrics and gynaecology, CCA - Cancer biology and immunology, Amsterdam Reproduction & Development (AR&D) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research cervical cancer Uterine Cervical Neoplasms Ligands Amphiregulin heparin-binding EGF-like growth factor Epiregulin 03 medical and health sciences 0302 clinical medicine Epidermal growth factor Cell Line Tumor Humans Growth factor receptor inhibitor RNA Messenger Epidermal growth factor receptor Autocrine signalling Chemokine CCL2 biology tumor-associated macrophages autocrine expression Granulocyte-Macrophage Colony-Stimulating Factor Articles Molecular biology ErbB Receptors Gene Expression Regulation Neoplastic Autocrine Communication 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research biology.protein Female epidermal growth factor receptor A431 cells Signal Transduction Transforming growth factor |
| Zdroj: | International Journal of Oncology International Journal of Oncology, 50(6), 1947-1954 International Journal of Oncology, 50(6), 1947-1954. Spandidos Publications Schrevel, M, Osse, E M, Prins, F A, Trimbos, J B M Z, Fleuren, G J, Gorter, A & Jordanova, E S 2017, ' Autocrine expression of the epidermal growth factor receptor ligand heparin-binding EGF-like growth factor in cervical cancer ', International Journal of Oncology, vol. 50, no. 6, pp. 1947-1954 . https://doi.org/10.3892/ijo.2017.3980 |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2017.3980 |
| Popis: | In cervical cancer, the epidermal growth factor receptor (EGFR) is overexpressed in 70-90% of the cases and has been associated with poor prognosis. EGFR-based therapy is currently being explored in cervical cancer. We investigated which EGFR ligand is primarily expressed in cervical cancer and which cell type functions as the major source of this ligand. We hypothesized that macrophages are the main source of EGFR ligands and that a paracrine loop between tumor cells and macrophages is responsible for ligand expression. mRNA expression analysis was performed on 32 cervical cancer cases to determine the expression of the EGFR ligands amphiregulin, β-cellulin, epidermal growth factor (EGF), epiregulin, heparin-binding EGF-like growth factor (HB‑EGF) and transforming growth factor α (TGFα). Subsequently, protein expression was determined immunohistochemically on 36 additional cases. To assess whether macrophages are the major source of EGFR ligands, immunohistochemical double staining was performed on four representative tissue slides. Expression of the chemokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and C-C motif ligand 2 (CCL2) was determined by mRNA in situ hybridization. Of the known EGFR ligands, HB‑EGF had the highest mRNA expression and HB‑EGF and EGFR protein expression were highly correlated. Tumor specimens with high EGFR expression showed higher numbers of macrophages, and higher expression of GM-CSF and CCL2, but only a small subset (9%) of macrophages was found to be HB‑EGF-positive. Strikingly, 78% of cervical cancer specimens were found to express HB‑EGF. Standardized assessment of staining intensity, using spectral imaging analysis, showed that HB‑EGF expression was higher in the tumor compartment than in the stromal compartment. These results suggest that HB‑EGF is an important EGFR ligand in cervical cancer and that cervical cancer cells are the predominant source of HB‑EGF. Therefore, we propose an autocrine EGFR stimulation model in cervical carcinomas. |
| Databáze: | OpenAIRE |
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