An important mediator of
tumorigenesis, the
epidermal growth factor receptor (EGFR) is expressed in almost all non-transformed cell types, associated with
tumor progression, angiogenesis and
metastasis. The significance of the EGFR as a
cancer therapeutic target is underscored by the clinical development of several different classes of EGFR antagonists, including
monoclonal antibodies (mAb) and
tyrosine kinase inhibitors. Extensive preclinical studies have demonstrated the anti-
tumor effects of mAb806 against
tumor xenografts overexpressing EGFR.
EGF stimulation of A431 cells induces rapid
tyrosine phosphorylation of intracellular signalling
proteins which regulate cell proliferation and apoptosis. Detailed understanding of the intracellular signalling pathways and components modulated by mAbs (such as mAb806) to EGFR, and other
growth factor receptors, remain limited. The use of fluorescence 2D difference gel electrophoresis (2D DIGE), coupled with sensitive MS-based
protein profiling in A431
tumor (
epidermoid carcinoma) xenografts, in combination with mAb806, revealed
proteins modulating endocytosis, cell architecture, apoptosis, cell signalling pathways and cell cycle regulation, including Dynamin-1-like
protein, cofilin-1
protein, and
14-3-3 protein zeta/delta. Further, we report various
proteins, including
Interferon-induced
protein 53 (IFI53), and Oncogene EMS1 (EMS1) which have roles in the tumor microenvironment, regulating
cancer cell invasiveness, angiogenesis and formation of
metastases. These findings contribute to understanding the underlying biological processes associated with mAb806
therapy of EGFR-positive
tumors, and identifying further potential
protein markers that may contribute in assessment of the treatment response.