A. De Luca was supported by a fellowship from Associazione Italiana per la Ricerca sul Cancro (AIRC).
The role of the EGFR signaling in tumor microenvironment†
Article first published online: 25 SEP 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 214, Issue 3, pages 559–567, March 2008
How to Cite
De Luca, A., Carotenuto, A., Rachiglio, A., Gallo, M., Maiello, M. R., Aldinucci, D., Pinto, A. and Normanno, N. (2008), The role of the EGFR signaling in tumor microenvironment. J. Cell. Physiol., 214: 559–567. doi: 10.1002/jcp.21260
- Issue published online: 20 DEC 2007
- Article first published online: 25 SEP 2007
- Manuscript Accepted: 23 JUL 2007
- Manuscript Received: 3 JUL 2007
- Associazione Italiana per la Ricerca sul Cancro (AIRC)
- Ministero della Salute. Grant Number: FSN 87/2005
The epidermal growth factor receptor (EGFR) family comprehends four different tyrosine kinases (EGFR, ErbB-2, ErbB-3, and ErbB-4) that are activated following binding to epidermal growth factor (EGF)-like growth factors. It has been long established that the EGFR system is involved in tumorigenesis. These proteins are frequently expressed in human carcinomas and support proliferation and survival of cancer cells. However, activation of the EGFR in non-malignant cell populations of the neoplastic microenvironment might also play an important role in cancer progression. EGFR signaling regulates in tumor cells the synthesis and secretion of several different angiogenic growth factors, including vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and basic fibroblast growth factor (bFGF). Overexpression of ErbB-2 also leads to increased expression of angiogenic growth factors, whereas treatment with anti-EGFR or anti-ErbB-2 agents produces a significant reduction of the synthesis of these proteins by cancer cells. EGFR expression and function in tumor-associated endothelial cells has also been described. Therefore, EGFR signaling might regulate angiogenesis both directly and indirectly. In addition, activation of EGFR is involved in the pathogenesis of bone metastases. Within the bone marrow microenvironment, cancer cells stimulate the synthesis of osteoclastogenic factors by residing stromal cells, a phenomenon that leads to bone destruction. It has been shown that EGFR signaling regulates the ability of bone marrow stromal cells to produce osteoclastogenic factors and to sustain osteoclast activation. Taken together, these findings suggest that the EGFR system is an important mediator, within the tumor microenvironment, of autocrine and paracrine circuits that result in enhanced tumor growth. J. Cell. Physiol. 214: 559–567, 2008. © 2007 Wiley-Liss, Inc.